Molecular and Cellular Mechanisms of Neural Circuit Assembly · 12:00-12:30 Temporal control of neurogenesis Bassem Hassan RLH 12:30-12:45 ... Regulation of Cerebral Cortex Folding

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Molecular and Cellular Mechanisms of Neural Circuit Assembly Klosterneuburg, Sebtember 11-14, 2017

Molecular and Cellular Mechanisms of Neural Circuit AssemblyKlosterneuburg, September 11-14, 2017

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Contents

1. About IST Austria ............................................................... 52. Program ............................................................................. 72.1 Abstract Overview ............................................................ 122.2 Abstracts .......................................................................... 193. General information ....................................................... 1013.1 Conference Dinner ....................................................... 102 3.2 Guided Tour ................................................................... 1034. Orientation & Transport ................................................. 104 4.1 Map of Klosterneuburg .................................................. 1054.2 Conference Location: Raiffeisen Lecture Hall (RLH, Building 02) ......................................................... 1064.3 Around IST Austria ......................................................... 1074.4 Hotels ............................................................................ 1084.5 Conference Shuttles ...................................................... 1094.6 Public Transportation to IST Austria .............................. 1104.7 Transportation in Vienna ............................................... 1134.8 Taxis ............................................................................... 1135. Contact & Organizing Committee .................................. 1155.1 Local Organizing Committee ......................................... 1165.2 List of Participants ......................................................... 117



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1. About IST Austria



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1. About IST Austria The Institute of Science and Technology Austria (IST Austria) is an in-ternational, multidisciplinary research institution dedicated to ba-sic research in the natural, computer and mathematical sciences. The Institute is located in the city of Klosterneuburg, 18 km from the cen-ter of Vienna. As a PhD granting institution, the graduate school at IST Austria educates doctoral students from diverse and international back-grounds with the aim of cultivating world-class research scientists. IST Austria was established jointly by the federal government of Austria and the provincial government of Lower Austria and inaugurated in 2009. Cur-rently, more than 570 employees from over 50 countries work at IST Austria. At present, the faculty of the institute consists of 46 professors. Following the implementation of the ambitious development plan, about 90 research groups will be working at IST Austria in a highly modern environment by 2026. To foster a creative and interdisciplinary scientific atmosphere, separating organizational structures, such as departments, are avoided at IST Aus-tria. The scientists are organized into independent research groups, each headed by a Professor or a tenure-track Assistant Professor. The decision to promote an Assistant Professor to Professor with a permanent contract is based entirely on an evaluation of the scientific achievements of the As-sistant Professor by international experts. Research excellence and promise are the exclusive hiring criteria for all scientists at IST Austria - from docto-ral students to professors. The Institute chooses which fields of science to enter based solely on the availability of outstanding individuals. It will pur-sue a direction of research only if it can compete with the best in the world.



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2. Program



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Time Program September 11th Speaker Room

08:00 Conference Shuttle 1 leaves from Wien Heiligenstadt - Hotel Höhenstraße Terrace

08:15 Conference Shuttle 2 leaves from Niedermarkt Klosterneuburg - Pension Alte Mühle Terrace

08:30 Conference Shuttle 3 leaves from Marienhof Terrace08:00-09:00 Registration Foyer 08:45 Welcome Address09:00 Session 1 - Chair: Alain Chetodal09:00-10:00 Keynote 1: Wiring Specificity: from Fly Olfactory

Circuit to Mouse Hippocampus Liqun Luo RLH

10:00-10:30 miRNAs in neuronal type specification: lessons from C. elegans

Luisa Cochella RLH

10:30-11:00 Generating layer-specific motion-direction sensitive neurons in Drosophila Iris Salecker RLH

11:00-11:30 Coffee Break Foyer

11:30-12:00Conserved mechanisms of axon guidance receptor sorting and signaling at the midline in fly and mouse

Greg Bashaw RLH

12:00-12:30 The mechanics of semaphorin-plexin cell guidance signaling

Yvonne Jones RLH

12:30-13:00 Probing Neural Receptor-Ligand Interactions Through Proteomics, Structure and Function

Engin Ozkan RLH

13:00-13:15Live monitoring reveals spatial and temporal codes of guidance receptor dynamics during commissural axon navigation

Aurora Pignata RLH

13:15-13:30Zic2 induces axon steering at the midline by increasing the levels of ß-catenin independently of the canonical Wnt signaling

Morenilla Cruz RLH

13:30-14:30 Lunch Break Cafeteria14:30 Session 2 – Chair: Uwe Drescher14:30-15:00 The adhesion GPCR Latrophilin and its neural

interaction partnersElena Seiradake RLH

15:00-15:15Prl-1 phosphatase controls spatial specificity of CNS synapse formation upstream of the InR/Akt/mTORC1 pathway

Oliver Urwyler RLH

15:15-15:30Signaling balance of Semaphorins and Neurotrophins controls the sexually dimorphic innervation of the mammary gland

Sar Shalom Hadas RLH

15:30-16:00 Myelin plasticity in health and disease Michelle Monje RLH


16:30-17:00 Studying myelinated axon formation and function using zebrafish David Lyons RLH

17:00-17:30 Molecular and genetic mechanisms of myelinating glial cell development Kelly Monk RLH

17:30-17:45 Development of retinotopy in the fly motion detection circuit

Filipe Pinto-Teixeira RLH



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17:45-18:00 Cooperation between retinal ganglion cells shapes the connectivity of the visual system Alice Louail RLH

18:00-18:15 Flash talks: each 2min RLH18:30-20:00 Dinner Cafeteria

20:00-22:00 Poster Session 1 (poster presenters with even numbers)

Mondi Hallway

22:00 Conference Shuttle 1 leaves for Hotel Höhenstraße - Wien Heiligenstadt Terrace

22:00 Conference Shuttle 2 leaves for Pension Alte Mühle - Niedermarkt Klosterneuburg Terrace

22:00 Conference Shuttle 3 leaves for Marienhof Terrace




08:30 Conference Shuttle 3 leaves from Marienhof Terrace09:00 Session 3 – Chair: Sarah Guthrie

09:00-10:00Keynote 2: The trajectory of forebrain GABA-ergic interneuron gene expression across development

Gordon Fishell RLH

10:00-10:30 Nutritional control of neural stem cells Andrea Brand RLH

10:30-11:00 Zika virus-associated microcephaly is caused by stress-induced unfolded protein response

Laurent Nguyen RLH


11:30-12:00Molecular mechanisms of neural stem cell lineage progression

Simon Hippen- meyer

RLH

12:00-12:30 Temporal control of neurogenesis Bassem Hassan RLH

12:30-12:45A multimodal single-cell approach identifies intercellular signaling networks in the developing human neocortex

Simone Mayer RLH

12:45-13:00Microdeletions in MAST1 cause mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations.

Ratna Tripathy RLH

13:00-13:15 Guidance of thalamic axons in the subpallium regulates cortical arealization

Alexander Sinclair- Wilson

RLH

13:15-13:30 Plexin-A1 and Semaphorin-6D are involved in retinal axon targeting

Alexandra Rebsam RLH

13:30-15:00 Lunch Break Cafeteria15:00 Session 4 – Chair: Robert Hindges15:00-15:30 Genetic evolution of cerebral cortex size

determinantsVictor Borrell RLH



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15:30-16:00Regulation of Cerebral Cortex Folding by Controlling Neuronal Migration via FLRT Adhesion Molecules

Rüdiger Klein RLH


16:30-17:00 Molecular pathways regulating quiescence of adult brain stem cells

Francois Guillemot RLH

17:00-17:15Stage-specific functions of Semaphorin7A during adult hippocampal neurogenesis rely on distinct receptors

Suzanne Lemstra RLH

17:15-17:30 Postnatal migration from the midbrain populates the thalamus with GABA interneurons

Alessio Delogu RLH

17:30-17:45 Superficial interneurons sharpen sensory maps during neonatal development

Natalia De Marco Garcia

RLH

17:45-18:00 Using cerebral organoids to study human interneuron migration

Joshua Bagley RLH

18:00-18:15 Flash talks: each 2min RLH 18:30-20:00 Dinner Cafeteria

20:00-22:00 Poster Session 2 (poster presenters with odd numbers)

Mondi Hallway







08:30 Conference Shuttle 3 leaves from Marienhof Terrace09:00 Session 3 – Chair: Rob Meijers

09:00-10:00Keynote 3: Development of neuronal diversity in the neocortex: from the embryo to 3D brain organoids

Paola Arlotta RLH

10:00-10:30 Building brain asymmetry: from genes to circuits Steve Wilson RLH

10:30-11:00 Axonal outgrowth and brain wiring: an RNA-cytoskeleton perspective

Claudia Bagni RLH

11:00-11:30 Coffee Break Foyer 11:30-12:00 A spatio-temporal GABAergic matrix in the

developing cortex of awake miceRosa Cossart RLH



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15:30-16:00Regulation of Cerebral Cortex Folding by Controlling Neuronal Migration via FLRT Adhesion Molecules

Rüdiger Klein RLH


16:30-17:00 Molecular pathways regulating quiescence of adult brain stem cells

Francois Guillemot RLH

17:00-17:15Stage-specific functions of Semaphorin7A during adult hippocampal neurogenesis rely on distinct receptors

Suzanne Lemstra RLH

17:15-17:30 Postnatal migration from the midbrain populates the thalamus with GABA interneurons

Alessio Delogu RLH

17:30-17:45 Superficial interneurons sharpen sensory maps during neonatal development

Natalia De Marco Garcia

RLH

17:45-18:00 Using cerebral organoids to study human interneuron migration

Joshua Bagley RLH

18:00-18:15 Flash talks: each 2min RLH 18:30-20:00 Dinner Cafeteria

20:00-22:00 Poster Session 2 (poster presenters with odd numbers)

Mondi Hallway







08:30 Conference Shuttle 3 leaves from Marienhof Terrace09:00 Session 3 – Chair: Rob Meijers

09:00-10:00Keynote 3: Development of neuronal diversity in the neocortex: from the embryo to 3D brain organoids

Paola Arlotta RLH

10:00-10:30 Building brain asymmetry: from genes to circuits Steve Wilson RLH

10:30-11:00 Axonal outgrowth and brain wiring: an RNA-cytoskeleton perspective

Claudia Bagni RLH

11:00-11:30 Coffee Break Foyer 11:30-12:00 A spatio-temporal GABAergic matrix in the

developing cortex of awake miceRosa Cossart RLH

12:00-12:15Removing the molecular brake on AMPA receptor synaptic accumulation leads to learning and memory deficits

Ines Gonza-lez-Calvo RLH

12:15-12:30Slitrk2 and Slitrk5 differentially control excitatory and inhibitory synapse formation on dopamin-ergic neurons and hyperactivity behavior

Charleen Salesse RLH

12:30-12:45 Astrocytic neuroligins control astrocyte neuropil infiltration and synaptic connectivity Jeff Stogsdill RLH

12:45-13:00 Endothelial control of motor axon pathfinding Dario Bonanomi RLH

13:00-13:30 Mechanisms of axon disassembly Marc Freeman RLH

13:30-14:30 Lunch Cafeteria14:30 Session 6 – Chair: Lynda Erskine

14:30-14:45 Autophagy controls interstitial axon branching of retinal ganglion cells Adnan Gee RLH

14:45-15:00 Sonic hedgehog guides axons through release of an Elmo-Dock complex

Fred Charron RLH

15:00-15:30 Novel stereotyped cell behaviours precede axon initiation in spinal neurons in vivo Jon Clarke RLH

15:30-16:00 Mechanisms of synaptic specificity underlying interneuronal circuit formation

Julia Kaltschmidt RLH

16:00-16:30 Coffee Break Foyer 16:30-16:45 Draxin recruits Netrin-1 to DCC to mediate

adhesion and axon guidanceTuhin Bhowmick RLH

16:45-17:00Dcc is required for somatotopic circuit development and topognosis in mice and humans.

Artur Kania RLH

17:00-17:30 Miniature neurotransmission is required for synapse maintenance during ageing

Brian McCabe RLH

17:30-18:00Restoring functional synaptic connectivity after synapse degeneration: a role for Wnt signalling in Alzheimer’s Disease

Patricia Salinas RLH

18:10-20:00 Conference Dinner at Redlinger Hütte Meeting Point: Terrace Walk to Redlinger Hütte (20 min )

20:30-24:00 Closing Reception IST Pub24:00 Conference Shuttle 1 leaves for Hotel

Höhenstraße - Wien Heiligenstadt Terrace

24:00 Conference Shuttle 2 leaevs for Pension Alte Mühle - Niedermarkt Klosterneuburg Terrace



08:00-16:00 Guided Tour to Dürnstein in the Wachau (UNESCO World Cultural Heritage)



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Poster

Nr.

Presenting

AuthorAffiliation Poster Title

1 Sarah Ackerman

University of Oregon

Astrocyte regulation of dendritic arbor complexity and synapse number

2 Gee Adnan

King‘s College London

Autophagy controls interstitial axon branching of retinal ganglion cells

3 Onno Akkermans

University of Oxford

Structural investigation of cell guidance receptors

4Sylvia Badurek

Vienna Biocenter

Mouse behaviour pipelines for various disease models

5 Joshua A Bagley

IMBA Using cerebral organoids to study human interneuron migration

6Robert Beattie

IST Austria

Mosaic analysis with double markers re-veals distinct sequential functions of Lgl1 in neural stem cells

7TuhinBhowmick

European Mo-lecular Biology Laboratory

Draxin recruits Netrin-1 to DCC to mediate adhesion and axon guidance

8Jenea Bin

University of Edinburgh

Novel regulator of axon caliber growth and nervous system function

9Dario Bonanomi

San Raffaele Scientific Ins-titute

Endothelial control of motor axon pathfinding

10 Bavat Bornstein

Weizmann Ins-titute of Science

Adhesion molecules play diverse roles during developmental neuronal remodeling

11Isabelle Brunet

INSERM U1050 - College de France

Sympathetic arterial innervation and Ephrina4/EPHA4 aignaling: Arteries under Pressure?

12LuisCarretero

University of Sussex

The α2-chimaerin signalling module and its role in oculomotor development and Duane Retraction Syndrome

13JulienCharest

IMP Establishment of neural left/right asymme-try through transcriptional priming in early embryonic lineages of Caenorhabditis elegans

2.1 Abstract Overview



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Poster

Nr.

Presenting


14 FredCharron

IRCM/McGill University

Sonic hedgehog guides axons through release of an Elmo-Dock complex

15Louis- Philippe Croteau

Institut de Recherches Cliniques de Montreal

Ephrin-A5 potentiates Netrin-1 signalling in spinal motor neurons.

16Divya Darwin Arulseeli

University Medical Center Utrecht

Area-specific innervation of dopaminergic neuron subsets in the developing midbrain

17NataliaDe Marco Garcia

Weill Cornell Medical College

Superficial interneurons sharpen sensory maps during neonatal development

18Danieldel Toro

Max Planck Institute of Neu-robiology

Regulation of cerebral cortex folding by controlling neuronal migration via FLRT adhesion molecules

19Alessio Delogu

King‘s College London

Postnatal migration from the midbrain populates the thalamus with GABA inter-neurons

20MariaDi Bonito

Institute of Bio-logy Valrose/Universite Nice Sophia Antipolis

Anatomical, molecular and functional characterization of rhombomere 4-derived sensorimotor subcircuit assembly in the mouse brainstem

21 Paula Dlugosz

Medical Univer-ity of Vienna

Evaluation of receptor interactions during Reelin signaling

22ChristianDuellberg

IST Austria Learning about the dual roles of α-Cen-taurin during neurogenesis from in vitro reconstitutions

23 AlexandreDumoulin

Max-Delbrueck-Center Berlin

cGMP signalling regulates S-palmitoylati-on in developing sensory neurons

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Xin-pengDun

Plymouth Uni-versity Pen-insula Schools of Medicine and Dentistry

Macrophage derived Slit3 controls the trajectories of cell migration in the periphe-ral nerve bridge to provide correct path for axon regeneration



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Poster

Nr.

Presenting


25AugustoEscalante


Elucidation of dorsal horn spinal circuits for somatosensory information

26EdwardGiniger

NIH (USA) Propulsion by Coherent Advance of Actin”: A novel mechanism of actin-based motility drives the growth of axons in vivo in the Drosophila wing

27CarlaGomes da Silva

University of Liege

Cell-intrinsic regulation of interneuron migration controls cerebral cortex morpho-genesis

28InésGonzález-Calvo

CIRB-College de France

Removing the molecular brake on AMPA receptor synaptic accumulation leads to learning and memory deficits

29Christian Hahn Dept. Bioelec-

tronics, ViennaOptical tssue clearing using stabilized organic media allows bleaching-free deep-tissue imaging of fluorescent whole mouse brain

30Baruch Haimson

The Hebrew University Hadassah Me-dical School

Genetic targeting and functional organiza-tion of spinocerebellar tract (CST) Inter-neurons

31Andi Hansen

IST Austria Cell-Autonomous and Non-Autonomous Mechanisms Controlling Projection Neuron Migration

32Yue He Karlsruhe Insti-

tute of Techno-logy

Alternative polyadenylation of odorant receptor mRNA upon wiring of mouse olfactory sensory neurons

33 Isabel Holguera

New York Uni-versity

Correlating neuronal birth order with circuit assembly in the Drosophila optic lobe

34Zengjin Huang VIB-KU Leuven

Center for Brain & Disease Research

Convergent evolution of clustered proto-cadherins (cPcdhs)

35Laura Jabinet

University of Zurich

The amyloid precursor protein APP collab-orates with Contactin2 during dI1 commis-sural axon guidance



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Poster

Nr.

Presenting


36Dominik Javorski

University of Vienna

A drosophila model of injury-induced synaptic plasticity

37 Alexander Jaworski

Brown University

Structure-function relationship of the multi-functional axon guidance receptor Robo3

38ArturKania

IRCM / McGill / U de Montreal

Dcc is required for somatotopic circuit development and topognosis in mice and humans.

39Rashmit Kaur

University of Vienna

Split-Brain in a fly: Developmental mecha-nism underlying bi-lateral nervous system organisation

40YvonneKölsch


Role of Slit-Robo signaling in the formation of retinotectal layers

41SuzanneLemstra

UMC Utrecht Stage-specific functions of Semaphorin7A during adult hippocampal neurogenesis rely on distinct receptors

42 DominikLindenhofer

IMBA Systematic analysis of human cerebral organoid growths

43AliceLouail

UPMC - Institut de la Vision

Cooperation between retinal ganglion cells shapes the connectivity of the visual system

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Søren S. L. Andersen

SciLifeLab, Uppsala University

Real time large scale in vivo observations reveal intrinsic synchrony, plasticity and growth cone dynamics of midline crossing axons during neuronal wiring of the zebra-fish spinal cord

45GrantMastick

University of Nevada

Slit/Robo signals control two guidance steps of oculomotor (III) and trochlear (IV) nerve growth to the eye

46Simone Mayer University of

CaliforniaA multimodal single-cell approach identifi-fes intercellular signaling networks in the developing human neocortex

47 OdedMayseless


Developmental coordination during olfac-tory circuit remodeling in Drosophila



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Poster

Nr.

Presenting


48OrenMeir


Characterization of neuronal circuits for coordinated wing flapping in avian

49 Olga Minkina


Neuron migration and neurite organization in the Drosophila optic lobe

50NataliaMora García

Institut du Cer-veau et de la Moelle Epinière

A temporal transcriptional switch governs neural stem cell division mode, neuronal numbers and maintenance of terminal differentiation

51 Giovanni Morelli

University of Liege

p27kip1 regulates axonal transport by modulating microtubules acetylation

52CruzMorenilla

Instituto de Neurocien-cias-UMH-CSIC

Zic2 induces axon steering at the midline by increasing the levels of ß-catenin inde-pendently of the canonical Wnt signaling

53Alexander Phillips

IMP Engineered cerebral organoids (enCORs) model effects of fetal alcohol exposure on cortical tissue architecture

54AuroraPignata

INMG - Uni-versité Claude Bernard Lyon

Live monitoring reveals spatial and tempo-ral codes of guidance receptor dynamics during commissural axon navigation

55Filipe Pinto- Teixeira


Development of retinotopy in the fly motion detection circuit

56ArianeRamaekers

ICM ”What big eyes you have”: a multiscale analysis of the logic and mechanisms of natural variation in eye size

57Fritz G.Rathjen

Max-Delbrueck-Center

The absence of sensory axon bifurcation affects sensory information processing and termination fields of afferents in the spinal cord

58 AlexandraRebsam

INSERM U839 - IFM

Plexin-A1 and Semaphorin-6D are invol-ved in retinal axon targeting



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Poster

Nr.

Presenting


59RomanRomanov

Center for Brain Research, Me-dical University of Vienna

Neuronal diversity of the hypothalamus: new subtype of hypothalamic dopamine neurons

60OriolRos


Studying axon guidance and neuronal migration with selective interference of second messenger function in vivo

61CharleenSalesse

Université Laval Slitrk2 and Slitrk5 differentially control excitatory and inhibitory synapse formation on dopaminergic neurons and hyperactivi-ty behaviour

62CarlosSanchez- Huertas

CRBM (CN-RS-UMR 5237)

Neuron Navigator-1 is an actin-binding microtubule plus-end tracking protein (+TIP) that controls the cyoskeletal dyna-mics in the neuronal growth cone.

63HadasSar Shalom


Signaling balance of Semaphorins and Neurotrophins controls the sexually dimor-phic innervation of the mammary gland

64Maria ChristinaSergaki

IMP GFRa1-dependent survival of cerebellar molecular layer interneurons is important for motor learning

65AlexanderSinclair- Wilson

ENS Guidance of thalamic axons in the subpal-lium regulates cortical arealization

66 Sophie Skarlatou

Max-Delbrueck-Center

Afadin disrupts central canal formation and gait selection

67JeffStogsdill

Duke University Astrocytic neuroligins control astrocyte neuropil infiltration and synaptic connec-tivity

68ReutSudakevitz


Collaterals patterning of dorsal spinal interneurons instructed by motor neurons-derived repulsive and V0-derived attractive cues

69 TraceySuter

Brown University

Meninges-derived cues control axon guidance



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Poster

Nr.

Presenting


70Takashi Suzuki

Tokyo Institute of Technology

Two receptor tyrosine phosphatases dicta-te the depth of the axon stabilizing layer in the Drosophila visual system.

71Ratna Tripathy

IMP Microdeletions in MAST1 cause mega-cor-pus-callosum syndrome with cerebellar hypoplasia and cortical malformations.

72 AlastairTulloch

Brown University

Genetic fate mapping of spinal commissu-ral neurons

73Olivier Urwyler

University of Zurich

Prl-1 phosphatase controls spatial speci-ficity of CNS synapse formation upstream of the InR/Akt/mTORC1 pathway

74 Eljovan Battum


Role of PlexinB2 in Cerebellar Granule Neuron Development

75 Danielle van Rossum

UMC Utrecht circular RNA‘s: novel regulators of neuro-nal development

76MariekeVerhagen

University Medical Centre Utrecht

Mouse genetics tools for studying Sema-phorin6A reverse signaling

77 MarkVerheijen

UMC Utrecht Dysregulation of circular RNAs and axonal defects in spinal muscular atrophy

78 RobinVigouroux


Identifying the role of DCC in the postnatal development of the visual system

79FrancoWeth

Karlsruhe Insti-tute of Techno-logy

Mechanisms of co-adaptation ensuring tar-geting precision in topographic guidance

80Kevin Wright

Vollum Institute, Oregon Health and Sciences University

Gbx2 regulates the development of a no-vel amacrine cell subtype in the mamma-lian retina



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2.2 Abstracts

P1

Tittle: Astrocyte regulation of dendritic arbor complexity and synapse number

Presenting Author: Sarah AckermanCo-Author(s): Marc Freeman, Chris Q Doe

Abstract: Astrocytes are major regulators of synaptic development and neu-ronal circuit function. My goal is to determine the signaling pathways used by astrocytes to establish and maintain specific, well-characterized neural circuits in the Drosophila CNS. I am performing in vivo manipulations of astrocytes, pre-synaptic neurons, and their post-synaptic partners (the tripartite synap-se) using newly developed transgenic lines that allow genetic manipulation of all three cell types within a behaviorally-relevant sensorimotor circuit. These tools allow visualization of defined neuron pairs and their synapses combined with an ability to simultaneously manipulate the associated astrocyte. Speci-fically, I am using traditional and optogenetic approaches to test the ability of astrocytes to remodel circuits in response to changes in neuronal activity. I’ve determined that acute activation of RP2 motoneurons within the larval CNS results in a significant decrease in dendritic arbor size and complexity. Ch-anges in neuronal activity have been shown to alter motoneuron arborization and synapse number at the neuromuscular junction. My data shows for the first time to our knowledge that altering motoneuron activity can alter the st-ructure of postsynaptic dendritic arbors within the CNS. Previous work in the developing visual system showed that mammalian astrocytes use the MEGF10/Draper pathway to engulf synaptically silenced synapses to refine retinoge-niculate connections. Drosophila astrocytes have also been shown to use this pathway to engulf neuronal debris after injury. I will test the hypothesis that astrocytes use the MEGF10/Draper pathway to not only engulf individual sy-napses, but to achieve large-scale remodeling of central dendritic arbors and in turn, changes in locomotor function. Using optogenetics to control the timing of the neuronal activity manipulation, I will determine how astrocytes instruct the establishment and/or maintenance of dendritic arbor size and complexity.



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P2

Title: Autophagy controls interstitial axon branching of retinal ganglion cells

Presenting Author: Gee AdnanCo-Author(s): Aine Rubikaite, Uwe Drescher

Abstract: Interstitial axon branching is an essential step during the establish-ment of neural connectivity in the vertebrate CNS. Here we have analysed the function of the small GTPase Arl8B in this process which is specifically located on lysosomes and controls their movement by acting as an adaptor protein to kinesin motors. We show that changing the level of expression of Arl8B in retinal ganglion cells affects both the relative position of branches along the axon as well as their number; that is a loss-of-function approach of Arl8B re-sults in a decrease, while a gain-of-function approach led to an increase in the number of RGC axon branches. In addition, knockdown and overexpression of Arl8B shifts axon branches to more proximal or distal parts of RGC axons, re-spectively. The synaptotropic hypothesis proposes a close link between presy-napse formation and axon branch formation, while investigations in Drosophila and in C. elegans have shown that presynapse formation is promoted by au-tophagy. We hypothesized that mechanistically Arl8B might regulate the num-ber and position of axon branches by controlling the movement of lysosomes to (or away from) autophagosomes which triggers autophagy and promotes presynapse formation. In support of this, we observed a partial overlap in the location of autophagosomes and lysosomes with presynaptic sites along retinal axons. Furthermore, we show that a disruption of autophagy either genetically or pharmacologically interferes with interstitial axon branching. Preliminary in vivo data suggest that inactivation of autophagy in subsets of retinal ganglion cells using a conditional KO approach results in a severe disruption of map formation in the retinocollicular projection. In sum, our data suggest that Arl8B plays a principal role in interstitial axon branching by controlling lysosome mo-bility, directing local autophagy, presynapse formation and interstitial branching.



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P3

Title: Structural investigation of cell guidance receptors

Presenting Author: Onno AkkermansCo-Author(s): Metin Aksu, Elena Seiradake

Abstract: During brain development, formation of complex network of neurons relies on an organized spatial and temporal signaling that is mediated by the interaction of a set of ligands and cell surface receptors. In contrast to the com-plexity of the network, only a number of receptor-ligand pairs has been attri-buted to this task. This implies that receptors work in a combinatorial fashion and/or that more receptors and ligands are yet to be identified. As we have recently shown with FLRT, Unc5 and Latrophillin, receptors and ligands can form large multimeric super complexes. These super complexes attenuate both attraction and repulsion responses, effectively expanding their signal spectrum and achieving complex signalling with a given number of receptors. The large size of this complex presents the opportunity to use electron microscopy to determine how this complex is in relation with the cell membrane. In this study, we present the preliminary negative stain analysis of such a super complex.



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P4

Title: Mouse behaviour pipelines for various disease models

Presenting Author: Sylvia BadurekCo-Author(s): Anna Jelem, Klaus Kraitsy

Abstract: In our core facility, we provide behavioral assays to answer ques-tions on disease models in mice. Beside other subjects, we address the field Learning and Memory as well as Anxiety and Depression. Symptoms of anxiety and depression or deficits in learning and memory can occur in-dependently. However, anxiety and depression-like symptoms can influence learning and memory function.We established pipelines to phenotype mouse lines, addressing questions on Learning and Memory as found in Alzheimer’s Disease or Dementia, congenital mental deficits as well as several cogniti-ve disorders. In another line of research we combine the TSE Phenomaster System, which is a highly flexible metabolic cage assembly, with well-known but also cutting-edge motoric assays. Thus, we established behaviour pi-pelines addressing Parkinson’s Disease models, but also models for stroke or traumatic brain injuries.Using the Phenomaster System, we developed another pipeline as well, which can be used for models addressing meta-bolic questions like thermoregulation, respiration or calory consumption.



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P5

Title: Using cerebral organoids to study human interneuron migration

Presenting Author: Joshua BagleyCo-Author(s): Daniel Reumann, Shan Bian, Julie Lévi-Strauss, Juergen A Knoblich

Abstract: Development of the forebrain involves the migration of GABAergic interneurons over long distances from subcortical into cortical brain regions. Although defects in interneuron migration are implicated in neuropsychiatric di-seases such as Epilepsy, Autism, and Schizophrenia, model systems to study this process in humans are currently lacking. To develop a suitable model sys-tem, we used a novel 3D cerebral organoid co-culture system to study human interneuron migration. We observed robust long-distance migration of interneu-rons from ventral into dorsal forebrain regions. These migrating interneurons can produce various interneuron subtypes, and live-imaging analysis shows features consistent with tangential interneuron migration. Moreover, reduced migration through drug-induced inhibition of chemotaxis receptors highlights the utility of this system for drug-screening. Therefore, our results demonstrate that cerebral organoid co-cultures can model complex interactions between different brain regions. Combined with reprogramming technology, this system offers a possibility to analyze complex neurodevelopmental defects using cells from neuropsychiatric disease patients, and to test potential therapeutic compounds.



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P6

Title: Mosaic analysis with double markers reveals distinct sequential functions of Lgl1 in neural stem cells

Presenting Author: Robert Beattie Co-Author(s): Maria Pia Postiglione, Laura E. Burnett, Susanne Laukoter, Carmen Streicher, Florian M. Pauler, Guanxi Xiao, Olga Klezovitch, Valera Vasioukhin, Troy H. Ghashghaei , Simon Hippenmeyer

Abstract: The concerted production of the correct number and diversity of neu-rons and glia is essential for intricate neural circuit assembly. In the developing cerebral cortex, radial glia progenitors (RGPs) are responsible for producing all neocortical neurons and certain glia lineages. We recently performed a quan-titative clonal analysis by exploiting the unprecedented resolution of the genetic MADM (Mosaic Analysis with Double Markers) technology and discovered a per-haps unexpected high degree of non-stochasticity and thus deterministic mode of RGP behavior. However, the cellular and molecular mechanisms controlling RGP behavior and proliferation dynamics in neurogenesis and glia generation remain unknown. To this end we identified Lgl1 as a critical regulatory compo-nent. By using a series of quantitative MADM-based experimental paradigms at single RGP resolution we found that Lgl1 non-cell-autonomously controls em-bryonic cortical neurogenesis. In contrast, Lgl1 is cell-autonomously required in early postnatal progenitors for producing the correct number of cortical astro-cytes. Lastly, Lgl1 controls adult neurogenesis in the postnatal subventricular stem cell niche via intrinsic cell-autonomous signalling. Collectively, our results obtained from single cell quantitative MADM analysis suggest that NSC-me-diated neuron and glia production is tightly regulated through the concerted interplay of sequential Lgl1-dependent global and cell intrinsic mechanisms.



25

P7

Title: Draxin recruits Netrin-1 to DCC to mediate adhesion and axon gui-dance

Presenting Author: Tuhin BhowmickCo-Author(s): Ying Liu, Yiqiong Liu, Xuefan Gao, Haydyn D T Mertens, Dmitri Svergun, Marina Michaylova, Junyu Xiao, Yan Zhang, Jia-huai Wang, Rob Meijers

Abstract: Netrin-1 is an evolutionarily conserved prototypical guidance cue - a secreted extracellular matrix protein involved in axon guidance at the central nervous system midline and known to trigger chemo-attraction by binding to its canonical receptor Deleted in Colorectal Cancer (DCC) (Keino-Masu et al., Cell. 87, 175–185, 1996). A recently discovered guidance cue Draxin was shown to bind DCC and cause chemorepulsion required for the development of spinal cord and forebrain commissures (Islam et al. Science. 323, 388-393, 2009). However, Gao et al. (Cell Reports. 12, 694-708, 2015) showed that Draxin can modulate Netrin-1 signaling. Here, we present the structural snapshots of Dra-xin/DCC and Draxin/Netrin-1 complexes using X-ray crystallography. The struc-tures of the molecular complexes reveal a triangle of interactions involving Ne-trin-1, Draxin and DCC through a “modular” binding mechanism utilizing multiple binding sites. Draxin can bind to DCC using a C-terminal cys-rich region, while a site towards its N-terminus can capture Netrin-1. Draxin facilitates Netrin-1 recruitment to DCC and may act as a modulator of Netrin-1/DCC mediated axon guidance. The observation fits well with the recent studies by Varadarajan et al. (Neuron. 94, 790-799, 2017) and Dominici C et al. (Nature. 545, 350-354, 2017), which suggest that rather than a freely diffusing gradient, it’s the accu-mulated Netrin-1 on the pial surface that directs axon growth along the adhesive surface. Together, these findings point towards a molecular mechanism invol-ving DCC, a single-pass membrane receptor that is used to link responses from different cues such as Netrin-1 and its modulator Draxin, creating a concerted guidance relay that governs the axon growth trajectory of a commissural neuron.



26

P8

Title: Novel regulator of axon caliber growth and nervous system func-tion

Presenting Author: Jenea BinCo-Author(s): Megan Madden, Daumante Suminaite, Silvia Benito, Linde Ke-gel, David A Lyons

Abstract: Axon caliber and myelination can both dramatically influence conduc-tion velocities along axons, and thus the function of neuronal circuits. Interes-tingly, it has also been suggested that both parameters can be dynamically re-gulated throughout life to fine-tune circuit function in order to meet precise timing requirements. Axon caliber itself contributes to the myelination fate of axons, but the mechanisms controlling axon caliber growth (and thus which axons become myelinated) in the central nervous system remain largely unknown. The larval zebrafish is an ideal model to study axon caliber due to its rapid development, optical transparency, and well defined neuronal circuitry, which allow for longi-tudinal, non-invasive imaging of readily identifiable neurons from initial axon outgrowth through integration into the circuit and subsequent refinement. In for-ward genetic screen, we identified a mutant with impaired axon caliber growth and hypomyelination. Our current analysis has focussed on the largest axon in the zebrafish spinal cord, the Mauthner axon, which grows to only half its nor-mal caliber in the mutant. Using transgenic reporters and live-imaging to follow individually labeled neurons in living zebrafish throughout circuit formation, we found that caliber growth is normal at the completion of axon outgrowth and on-set of myelin formation, but significantly slows thereafter. This results in reduced conduction velocities and hypomyelination along the Mauthner axon. As the Mauthner axon is a critical component of the neuronal circuit required for esca-pe responses, we expected these changes to slow escape behaviours. Surpri-singly, the latency to escape response in mutants was normal, and furthermore, mutants exhibited increased sensitivity to stimuli and faster swim velocities. We are now taking a more in depth look at the neuronal circuitry in our mutant to un-derstand these changes. We are also beginning to unravel the novel mechanism by which our mutation influences axon caliber growth during circuit formation.



27

P9

Title: Endothelial control of motor axon pathfinding

Presenting Author: Dario BonanomiCo-Author(s): Raluca Marcu, Ganesh Bhat, Aurora Badaloni, Karen Lettieri, Joseph Lewcock, Yutaka Yoshida, Samuel Pfaff

Abstract: Neurons and blood vessels are functionally interdependent and ana-tomically coupled. This association is critical for nervous system physiology and its disruption is a hallmark of neurological disorders. However, the mo-lecular pathways underlying nerve-vessel communication are poorly under-stood and it is unclear whether neurovascular interactions are instructive for the assembly of neuronal and vascular networks. In a forward genetic screen based on mouse ENU-mutagenesis, designed to uncover recessive genes af-fecting development and connectivity of spinal motor neurons, we identified the Drake allele, which disrupts motor axon projections. This mutation was map-ped to the Plexin-D1 gene that encodes for a Semaphorin receptor involved in vascular morphogenesis and neuronal guidance. Drake causes Plexin-D1 loss-of-function, generating a signaling-deficient receptor with aberrant mem-brane targeting and incompetent for ligand binding. At the embryonic stages when axon guidance defects arise in Drake mutants, Plexin-D1 is enriched in endothelial cells, whereas it is undetectable in motor neurons. Conditional deletion of Plexin-D1 gene in the endothelium, but not motor neurons, phe-nocopies Drake mutants, demonstrating that axon targeting defects are non-cell autonomous, originating from defective Plexin-D1 signaling in endothelial cells. Interestingly, the canonical Plexin-D1 ligand, Sema3E, is dispensable for endothelial-dependent control of motor projections, pointing to alterna-tive ligands or a non-conventional signaling mode. In vivo and in vitro studies support that Plexin-D1 controls the spatial relationship of motor neurons and endothelial cells during development. We propose that endothelial cells function as guideposts that convey positional information critical for axon pathfinding.



28

P10

Title: Adhesion molecules play diverse roles during developmental neuronal remodeling

Presenting Author: Bavat BornsteinCo-Author(s): Oren Schuldiner

Abstract: Neuronal remodeling, by which neuronal connection are refined, is essential for the proper development of vertebrate and invertebrate ner-vous systems. Developmental neuronal remodeling encompasses processes that include pruning of exuberant axons and dendritic branches, which may regrow to form new, adult specific, connections. The stereotypical neuronal re-modeling of the Drosophila mushroom body (MB) ? neurons offers a unique opportunity to study the mechanisms of developmental axon pruning as well as developmental axon regrowth. Even though remodeling of MB ? neurons was described almost twenty years ago, our understandings of the underlying cellular and molecular mechanisms are still incomplete. We have recently shown that destabilization of the adhesion molecule FasciclinII (FasII), the or-tholog of the neural cell adhesion molecule (NCAM), is an important step is promoting axon pruning. Interestingly we found that FasII downregulation is required only for axon but not for dendrite pruning of MB ? neurons. These results, imply that differential regulation of adhesion molecules might play an important role in regulating the spatial dynamics of developmental axon re-modeling. In order to identifying novel cell adhesion molecules (CAMs) that are important for MB neuronal remodeling we conducted a mini-screen of candidate CAMs of the immunoglobulin superfamily (IgSF). In order to pin-point relevant candidates, we used RNAseq methodology to uncover the ex-pression patterns of these CAMs in MB ? neurons during development and found over 70 candidate CAMs that are expressed at detectable levels within the MB. Preliminary work highlighted two protein subfamilies, the Beat and the Dpr families, as important for different spatial aspects of neuronal remo-deling. Taken together these results underline the importance of cell adhesi-on in regulating the spatial dynamics of developmental axon remodeling.



29

P11

Title: Sympathetic arterial innervation and EphrinaA4/EPHA4 Signaling: Arteries under pressure?

Presenting Author: Isabelle BrunetCo-Author(s): Simonnet E., Martin S., Vilar J., Pardanaud L., Eichmann A., Sylvestre J.-S

Abstract: Arteries receive a sympathetic innervation which is crucial to control their contraction level. Sympathetic nerves establish „“en passant““ synapses, called neurovascular junctions with arterial smooth muscle cells. Gene expres-sion comparison of non-innervated and innervated arteries revealed that the re-pulsive axon guidance molecule EphrinA4 is surprisingly expressed by arteries ar the onset of innervation (Postnatal day 2 P2). We here investigated the role of EphrinA4 signalization in the development and physiology of arterial innervation in mice. We showed by immunostaining and in situ hybridization that EphrinA4 is expressed by smooth muscle cells of resistance arteries and identified its receptor EphA4, expressed by sympathetic neurons. Binding and collapse ex-periments showed that EphrinA4 mediates the collapse of sympathetic growth cones in vitro via EphA4. EphrinA4 KO and EphA4 KO mice exhibited an in-creased arterial innervation at P2, consistent with a loss of repulsion. We then generated EphA4 flox-TH CRE mice who exhibited the same enhanced arterial innervation at P2 , which interestigly remained in adult mice. Increased arterial innervation in EPhA4 flox-TH CRE mice was correlated with a higher number of neurovascular junctions and a modifcation of their structure visible by eletronic microscopy. Measurement of cutaneous blood flow using laser doppler revealed an enhanced vasoconstriction in this mice. Resistivity and pulstility index of ca-rotids calculated from ultrasound views were increased, suggesting enhanced vascular resistivity. Thus EphrinA4 expressed by arterial smooth muscles cells induces collapse of sympathetic growth cones via the receptor EphA4 to refine sympathetic arterial innervation. Impairment of EphrinA4/EphA4 signaling leads to increased arterial innervation, vascular resistance and vasoconstriction. As systemic blood pressure depends on cardiac output but also vascular re-sistance, we are currently testing if those functional defects could lead to hyper-tension from sympathetic origin, or at least aggravate pre-existing hypertension.



30

P12

Title: The α2-chimaerin signalling module and its role in oculomotor de-velopment and Duane Retraction Syndrome

Presenting Author: Luis CarreteroCo-Author(s): Ragnheidur Gudjonsdottir, Ivana Poparic, Marco Chiapello, Mi-chael Deery, Sarah Guthrie

Abstract: Around 1% of the human population suffers from an eye movement disorder, commonly referred to as squint, which in severe cases can result in amblyopia and partial blindness. Eye movements depend on the ocular motor system, which consists of three cranial motor nerves and six muscles and is conserved across vertebrates, including human, mouse, chicken and zebrafish. A congenital form of squint - Duane retraction syndrome (DRS) – is caused by mutations in the signalling protein alpha2-chimaerin (α2-chn). α2-chimaerin is a Rac-GAP which is involved in several axonal guidance signalling pathways and neuroimaging has shown that DRS patients with α2-chn mutations have abnor-mal wiring of the ocular motor system. The key to understanding the causation of DRS therefore lies in dissecting out the molecular components of α2-chimaerin signalling pathways in neurons, and in determining how changes in the pattern of these interactions lead to DRS. In this work, we used a proteomics approach to identify α2-chn binding partners that show differential binding between wild-type and mutant protein isoforms. We then used the zebrafish as a model to stu-dy the signalling pathways of α2-chimaerin and other signalling partners using loss and gain of function approaches, neuroanatomy and behavioural analysis. We have identified possible α2-chn binding partners that cause axon guidance defects when manipulated in vivo, that modify eye movements, and that may lie downstream of α2-chn during ocular motor development.



31

P13

Title: Establishment of neural left/right asymmetry through transcriptio-nal priming in early embryonic lineages of Caenorhabditis elegans

Presenting Author: Julien CharestCo-Author(s): Thomas Daniele, Luisa Cochella

Abstract: „Despite presenting an overall bilaterally symmetric anatomy in most animals, nervous systems display left/right asymmetries in the way they sense and process information. In humans, higher brain functions such as language are lateralized. However, the ontogenic events responsible for neural asymme-try are poorly understood. C. elegans is to date the only organism in which a directed functional left/right asymmetry in a pair of sensory neurons, the ASEs, correlates with asymmetric gene expression. Although morphologically symme-tric, the ASEs arise from lineages diverging at the 4-cell stage embryo. At that early stage, transient expression of the transcription factors TBX-37/38 restric-ted to the blastomere from which the left ASE neuron originates, primes a miR-NA locus for its later high level expression that defines the “left” fate. While this transcriptional priming event is key for the molecular and functional asymmetry between the left and right ASE neurons, it is unknown if it represents a broader mechanism for generating neuronal diversity. Given that TBX-37/38 are expres-sed in precursors giving rise to an additional 10 left neurons that are members of bilateral pairs, we suggest that transcriptional priming of other terminal dif-ferentiation loci might be employed to introduce molecular asymmetries within these neuron pairs and increase neuronal diversity in C. elegans. Using a com-bination of ChIP-seq, RNA-seq and molecular reporters for gene expression, we aim to investigate further neuronal asymmetries in the worm’s nervous system as well as further understand the molecular basisresponsible for lateralization.



32

P14

Title: Sonic hedgehog guides axons through release of an Elmo-Dock complex

Presenting Author: Fred CharronCo-Author(s): S. Makihara, S. Morin, J. F. Cote, P. T. Yam

Abstract: In the developing spinal cord, Sonic hedgehog (Shh) attracts commis-sural axons toward the floorplate. How Shh regulates changes in the growth cone cytoskeleton, in particular, the guanine nucleotide exchange factor (GEF) acting downstream of Shh, remains unknown. We found that Shh activation of the RhoGTPase Rac1 required the activity of Dock, an unconventional Rho GEF. Knockdown of Dock3 and 4, or its binding partner Elmo1 and 2, abolis-hed commissural axons attraction by Shh in vitro. Importantly, Dock and Elmo activity were also required for correct commissural axon guidance in vivo. We show that Dock and Elmo interact with Boc, the Shh receptor, and that this interaction is reduced upon stimulation with Shh. Furthermore, Shh stimula-tion translocates Elmo to the growth cone periphery. Based on these results, we propose a model where Shh stimulation releases the Dock/Elmo complex from Boc, thus allowing Dock/Elmo to regulate RhoGTPase activity in axon gui-dance. These results reveal how Shh can modulate cytoskeletal reorganization in growth cones, and identify new mediators of non-canonical Shh signaling.



33

P15

Title: Ephrin-A5 potentiates Netrin-1 signalling in spinal motor neurons

Presenting Author: Louis-Philippe CroteauCo-Author(s): Daniel Morales, Tzu-Jen Kao, Artur Kania

Abstract: Axon guidance cues act in concert, but the molecular mechanisms un-derlying such interactions remain obscure. A subpopulation of limb-innervating axons of lateral motor column (LMC) motor neurons prefers to grow on Netrin-1 and is repelled from ephrin-A5. We previously showed that Neogenin medi-ates LMC axon Netrin-1 growth preference and that Netrin-1 and ephrin-A5 guide LMC axons synergistically. To gain insight into the mechanism controlling such synergy, we used fluorescence immunohistochemistry and enrichment for cell surface proteins, to show that ephrin-A5 stimulation results in an increa-se in Neogenin surface protein levels in LMC growth cones, and concomitant increase in Netrin-1 binding. This effect is enhanced by overexpression of the ephrin-A5 receptor EphA4 and is prevented by the inclusion of a peptide that in-hibits ephrin-A5-EphA4 binding, implicating ephrin-A:EphA signalling in increa-sing Neogenin at the growth cone. Since overexpression of EphA4 lacking its intracellular domain also increases Neogenin levels we are exploring the possi-bility that extracellular protease cleavage could mediate this effect. As functional evidence for the ephrin-A5 induced sensitization of LMC axons, bath addition of ephrin-A5 increases the outgrowth of LMC axons on Netrin-1, while the reverse manipulation has no effect. Our results suggest a novel interaction between the ephrin:Eph and Netrin signalling pathways. Given their roles in neural circuit development and synaptic function, as well as in angiogenesis, bone homeos-tasis and cancer, our observations could have implications for our understan-ding of diverse biological processes within and outside the nervous system.



34

P16

Title: Area-specific innervation of dopaminergic neuron subsets in the developing midbrain

Presenting Author: Divya Darwin ArulseeliCo-Author(s): Sara Brignani, Ewoud R. E. Schmidt, Eljo van Battum, Youri Adolfs, R. Jeroen Pasterkamp

Abstract: The midbrain dopaminergic system is known to be involved in con-trol of voluntary movement and reward-motivation behaviors. It comprises of anatomically, functionally distinct dopamine neuron subtypes with specific gene expression profiles and axonal connectivity. While it is known that a subset of dopaminergic neurons belonging to the substantia nigra pars compacta (SNc) project to the dorsal striatum and those of the ventral tegmental area (VTA) pro-ject to the ventral striatum, prefrontal cortex and limbic areas, it is unclear how this preferential innervation is developmentally regulated. This is because we lack model systems to distinguish dopamine neurons subsets and their axons during early developmental stages. In this study, we generated and characte-rized specific mouse models that label preferentially SNc or VTA neurons and understand their topographic preference for innervation during embryonic de-velopment. We show that the area-specific innervation of dopaminergic neuron subtypes is preserved already during early development and is likely regulated by guidance mechanisms rather than by postnatal pruning, as reported pre-viously. The mouse models generated provide crucial tools for understanding developmental functional organization in the dopamine system, positional cues that guide this organization and neurodegenerative changes during aging.



35

P17

Title: Superficial interneurons sharpen sensory maps during neonatal development

Presenting Author: Natalia De Marco GarciaCo-Author(s): Alicia Che, Rachel Babij, Andrew Iannone, Robert Fetcho, Moni-ca Ferrer, Conor Liston, Gord Fishell

Abstract: Neuronal connectivity and specific circuit configurations are funda-mental for proper information processing, and the balance between inhibition and excitation is critical in establishing precise functional circuits. In developing sensory cortices, the interaction between sensory experience and synapse for-mation is essential for sculpting circuit connectivity. However, how early sensory inputs regulate the proper integration of excitatory cells and inhibitory interneu-rons into nascent networks is poorly understood. Here we used two-photon in vivo calcium imaging and mono-synaptic rabies viral tracing to reveal the source of inputs that control the assembly of neuronal networks in the murine barrel cortex. We genetically labeled neuronal subtypes present in superficial layers, and analyzed the spatio-temporal features of calcium-mediated activity in a chronic in vivo preparation in young mice. We found that Reelin-expressing interneurons derived from the caudal ganglionic eminence (Re CGE) display long, highly correlated calcium events during the first postnatal week and that this activity pattern becomes drastically decorrelated as the cortex matures. In contrast, neither VIP-expressing interneurons nor those derived from the medial ganglionic eminence (MGE) show phase-locked oscillations during the first post-natal week. Intriguingly, thalamic axons within superficial layers also experience calcium transients with similar temporal dynamics to those of Re CGE interneu-rons. Furthermore, we show that Re CGE interneurons receive transient thalamic inputs and that these inputs shape their network dynamics during the first post-natal week. Remarkably, silencing the output of this population causes aberrant sensory map formation in the barrel cortex. Thus, our results indicate that sen-sory inputs selectively recruit Re CGE interneurons providing necessary drive for their network integration at early postnatal stages. In turn, Re CGE interneu-ron activity is required for the proper structural development of the barrel cortex. Given the accumulating experimental evidence implicating interneuron dysfunc-tion in brain disorders, understanding the mechanisms underlying activity-depen-dent plasticity and how circuit dynamics are established for these interneurons can provide invaluable insights for the development of therapeutic strategies.



36

P18

Title: Regulation of cerebral cortex folding by controlling neuronal mig-ration via FLRT adhesion molecules

Presenting Author: Daniel del ToroCo-Author(s): Tobias Ruff, Erik Cederfjäll, Ana Villalba, Gönül Seyit-Bremer, Víctor Borrell, Rüdiger Klein

Abstract: The folding of the mammalian cerebral cortex into sulci and gyri is thought to be favored by the amplification of basal progenitor cells and their tan-gential migration. Here we provide a molecular mechanism for the role of migra-tion in this process by showing that changes in intercellular adhesion of migra-ting cortical neurons result in cortical folding. Mice with deletions of FLRT1 and FLRT3 adhesion molecules develop macroscopic sulci with preserved laye-red organization and radial glial morphology. Cortex folding in these mutants does not require progenitor cell amplification, but is dependent on changes in neuron migration. Analyses and simulations suggest that sulci formation in the absence of FLRT1/3 results from reduced intercellular adhesion, increased neuron migration and clustering in the cortical plate. Notably, FLRT1/3 expres-sion is low in the human cortex and in future sulcus areas of ferrets, suggesting that intercellular adhesion is a keyregulator of cortical folding across species.



37

P19

Title: Postnatal migration from the midbrain populates the thalamus with GABA interneurons

Presenting Author: Alessio DeloguCo-Author(s): J. Polona, O. Brock, Z. Xie, T.M. Jessell, S. Brickley

Abstract: Thalamic inhibition has long been modelled on the existence of two cell types: reticular and intrinsic interneurons. Both inhibitory types have long been seen as having a prethalamic origin, with the local interneuron subtype migrating tangentially to seed thalamo-cortical relay nuclei with inhibitory cells after birth. Here we present experimental evidence in support of a radically different model. Using fate-mapping, time lapse imaging and conditional gene inactivation, we show that most thalamic GABA interneurons are specified in the dorsal midbrain - an evolutionarily distinct brain region. The Sox14/Gata2/Otx2-expressing precur-sor cells migrate in a caudo-rostral direction to populate the visual thalamus and other relays with GABAergic interneurons. This unexpected extra-diencephalic origin distinguishes local interneurons from other intrinsic GABAergic populati-ons of the thalamus. Connectivity mapping of distinct thalamic GABA populati-ons reflects their diverse origins and suggests different functional specialization.



38

P20

Title: Anatomical, molecular and functional characterization of rhombo-mere 4-derived sensorimotor subcircuit assembly in the mouse brainstem

Presenting Author: Maria Di BonitoCo-Author(s): Eya Setti, Luis Puelles, Michèle Studer

Abstract: The sensorimotor circuits are established during development and depend on spatially- and temporally-ordered sequence of neuronal specifica-tion, migration and connectivity. Cell lineage studies have started to correla-te early rhombomeric subdivisions to adult neuronal connectivity maps in the brainstem indicating that regional patterning along the anteroposterior (AP) axis and neuronal subtype specification along the dorsoventral (DV) axis in-tersect to specify neuronal fates. Besides conferring AP identity during hind-brain segmentation, Hox genes regulate specification, neuronal migration, axon pathfinding as well as topographic connectivity of different sensorimo-tor neurons along the DV axis in a rhombomere-specific manner. We have used a b1r4-Cre mouse line to genetically label rhombomere 4 (r4), and to characterize all r4-derived neuronal populations and axonal tracts from their embryonic origin to their final adult location and targets. We demonstrate that a rhombomere-specific Hox code controls the assembly of distinct functionally subcircuits in the developing auditory system. R4 contributes to sound trans-mission and amplification pathways, and to the establishment of two efferent feedback subcircuits involved in the protection from acoustic overstimulation. In addition, r4 gives rise to the vestibulospinal projection neurons that convey vestibular information to limb-related spinal motor circuits, and contributes to the topographic trigeminal pathway to the thalamus via the r4-derived spinal trigeminal oral subnucleus. Moreover, Hoxb1 represents a key developmental gene playing a crucial role in the establishment of regional identity of motor and sensory neurons in r4-derived subcircuits. Hoxb1 promotes an r4-speci-fic developmental program partially by repressing r3-like molecular and neuro-nal features and inhibiting Hoxa2, Atoh1, and Ascl1 expression in the different sensorimotor systems. Finally, thanks to the generation of a novel r4-Flippase mouse and the use of several DV subtype-specific Cre-recombinase lines, we aim to employ an intersectional genetic strategy to dissect the molecular and cellular mechanisms allowing proper neuronal cell fate specification, migration and connectivity of distinct sensorimotor subpopulations originating from r4.



39

P21

Title: Evaluation of receptor interactions during Reelin signaling

Presenting Author: Paula DlugoszCo-Author(s): Roland Tresky, Johannes Nimpf Abstract: The extracellular matrix molecule Reelin plays a central role in mi-gration and positioning of neurons in the cortex, hippocampus and cerebel-lum during embryogenesis. Reelin is also expressed in the adult brain and it enhances long-term potentiation. Additionally, it has a neuroprotective role in Alzheimer’s disease. The canonical Reelin signaling pathway starts with bin-ding of Reelin to apolipoprotein E receptor 2 (ApoER2) and very low-density lipoprotein receptor (VLDLR), which triggers Src-family kinase induced tyrosi-nephosphorylation of the intracellular adaptor protein disabled-1 (Dab1). The current model suggests that binding of Reelin results in receptor oligomerization and subsequent clustering of Dab1. Until now the size and nature of receptor clusters induced by Reelin binding is unknown. Oligomerization state of Apo-ER2 and VLDLR upon Reelin binding was analyzed using time-resolved anisot-ropy (homo-FRET) for homooligomerization and Fluorescence Lifetime Imaging Microscopy (FLIM-FRET) for heterooligomerization. Homo-FRET and He-tero-FRET FLIM studies indicate that ApoER2 and VLDLR form homo-/hetero-dimers or higher order oligomers even in the absence of the ligand. The central region of Reelin induces ApoER2 homooligomerization which occurs within a few minutes after Reelin stimulation. VLDLR/ApoER2 heterooligomerization is much slower and does not occur before 15 min after Reelin stimulation.VLDLR selectively heterooligomerizes with the hypo-glycosylated variant of ApoER2 and not with the fully glycosylated form of ApoER2 which is exclusively present in lipid raft domains of the cell membrane. A splice variant of ApoER2 present in the brain lacking the O-linked sugar domain does also interact with VLDLR.



40

P22

Title: Learning about the dual roles of α-Centaurin during neurogenesis from in vitro reconstitutions

Presenting Author: Albert AuerCo-Author(s): Christian Duellberg, Martin Loose

Abstract: Two key steps during neurogenesis are neurite outgrowth followed by a break in cellular symmetry, which gives rise to a neuron with distinct com-partments called axon and dendrites. How these processes are coordinated is only partly understood. One important player for both of these distinct steps is α-Centaurin (gene:ADAP1). This protein was found to have two important func-tions: first, it was found to deactivate the small GTPase ARF6, which is involved in membrane trafficking and cytoskeleton organization. Second, it contains two PH domains, where one was found to have a high affinity for PIP3 and the other binds to motor proteins of the Kif13 family. Accordingly, ADAP-1 might be involved in the transport of PIP3-containing vesicles, thereby contributing to an asymmetric distribution of PIP3 in the nascent axon, which was found essential for persistent PIP3 enrichment during axon specification in hippocampal cell cul-ture systems. In this project, we aim to understand the role of ADAP during neu-rite outgrowth and neuronal symmetry breaking. Using an in vitro reconstitution approach based on purified components, we aim to rebuild the regulated PIP3 transport feedback loop involving KIF13B, α-Centaurin and its potential regula-tors. At the same time, we want to study the requirements for α-Centaurins GAP activity on the ARF6 GTP cycle. Together, this will allow us to dissect potential cross talk between these two distinct processes, to improve our mechanistic un-derstanding of PIP3 amplification as well as of the molecular basis of how neurite outgrowth and axon specification during early neuronal development. Abbrevia-tions: GTP: Guanosine-5‘-triphosphate, ARF6: ADP-ribosylation factor 6 , PIP3: Phosphatidylinositol (3,4,5)-trisphosphate, GAP: GTPase-activating protein.



41

P23

Title: cGMP signalling regulates S-palmitoylation in developing sensory neurons

Presenting Author: Alexandre DumoulinCo-Author(s): Gohar Ter-Avetisyan, Hannes Schmidt, Alina Dagane, Gunnar Dittmar, Fritz G. Rathjen

Abstract: We previously demonstrated that a cGMP signalling cascade is invol-ved in the bifurcation of dorsal root ganglia (DRG) and cranial sensory ganglia axons when entering the spinal cord or hindbrain, respectively. Each component of this cascade is needed for axonal bifurcation: the C-type natriuretic peptide, which binds to the natriuretic peptide receptor 2 (Npr2), a particulate guanylyl cy-clase that produces cGMP from GTP, and the cGMP-dependent kinase I (cGKI) which is a serine/threonine kinase. When one of those components is missing, sensory axons are not able to bifurcate anymore but are instead forming turns. In view of this, we investigated downstream events of this cGMP signalling casca-de in order to characterize in more details by which mechanism axon bifurcation of sensory neurons is mediated in the mouse embryo. Using cultured embryonic DRG we showed that the Npr2-mediated cGMP signalling is implicated in a GC remodelling leading to its enlargement that is triggered by cGKI. It was found to be compartmentalized close to intracellular membranes mostly in the central (C)-domain of the GC suggesting a regulation of peripheral membrane protein trafficking. Moreover, the same signalling cascade appeared to remodel the adhesome at the cultured DRG plasma membrane supporting this idea.We the-refore speculated that S-palmitoylation might play a role downstream of cGKI. Interestingly, biorthogonal labelling of palmitoylated proteins and click chemistry revealed an enrichment of the palmitoylated proteins within the C-domain of the GC in cultured DRG neurons. Moreover, those palmitoyl-rich structures overlap-ped to cGKI-positive structures suggesting an interplay between cGKI-media-ted phosphorylation and S-palmitoylation. Indeed, cell culture experiments as well as a biochemical approach confirmed that S-palmitoylation plays a central role downstream of cGKI in this system.Our findings reveal the essential role of S-palmitoylation in the development of DRG axons in culture and suggest a role in vivo by being implicated in the GC plasma membrane expansion that might be a prerequisite for the GC splitting and bifurcation. Moreover, it also pinpoints and put the light on the central role that might have phosphorylation in regulating protein S-palmitoylation inside but also outside the nervous system.



42

P24

Title: Macrophage derived Slit3 controls the trajectories of cell migration in the peripheral nerve bridge to provide correct path for axon regenera-tion

Presenting Author: Xin-peng DunCo-Author(s): Lauren Carr, Louisa K. Drake, David B. Parkinson

Abstract: The Slit-Robo signalling has been well characterized as a repulsive si-gnalling for precise axon pathfinding and neuronal migration during embryonic development. Slit1-3 and Robo1-2 are highly expressed in the adult peripheral nervous system and they are differentially and topologically regulated after pe-ripheral nerve injury. However, a possible function of the Slit-Robo signalling in peripheral nerve repair is currently unclear. Using the mouse sciatic nerve tran-section as a research model, we have studied the dynamic expression pattern of Slit1-3 and Robo1-2 after peripheral nerve injury. In particular, we found that macrophages form the outermost layer of the nerve bridge and secrete high levels of Slit3 while migratory cells and regenerating axons inside the nerve bridge express high levels of Robo1. In line with the Slit3 and Robo1 expression pattern, we observed axon regeneration and cell migration defects in the nerve bridge in Slit3 and Robo1 gene mutant mice. Our findings have revealed a novel function for macrophages in the PNS, regulating Slit3-Robo1 signalling pathway to control correct peripheral nerve bridge formation and precise axon targeting.



43

P25

Title: Elucidation of dorsal horn spinal circuits for somatosensory information

Presenting Author: Augusto EscalanteCo-Author(s): Rüdiger Klein

Abstract: Spinal neurons in the dorsal horns are the first relay center for se-veral modalities of somatosensory information. Sensory neurons are located in the dorsal root ganglia and innervate each centimeter of our ca. 2 m2 of skin. They transmit pain, temperature, itch and mechanical information to the central nervous system via the spinal dorsal horns. In the last few years, se-veral reports have highlighted the importance of genetically identified spinal subpopulations of neurons in the transmission and gating of incoming senso-ry information into the central nervous system (Duan et al., 2014; Bourane et al., 2015; Foster et al., 2015). However, the requirement of the dorsal horns themselves in somatosensory processing remain unclear given the existence of direct connections from sensory neurons to the dorsal column nuclei. Here, using transsynaptic viral tracing and intersectional genetics to specifically target spinal cord neurons, sparing hindbrain, midbrain and forebrain structures, we manipulated the two main classes of neuronal populations in the dorsal horns: inhibitory or dILA and excitatory or dILB (Muller et al., 2002; Gross et al., 2002; Helms, 2003). Viral tracing allowed us to define different modalities of sensory and supraspinal synaptic inputs received by each spinal type. Intersectional restriction of fluorescent reporters let us trace the brain areas targeted by each class of neurons demonstrating the existence of a map of common and also class-specific patterns of innervation. Finally, behavioral analysis of animals in which dILA or dILB neurons had been specifically ablated was conducted to assess somatosensory deficits. Both populations seem to be required for the correct interpretation of different sensory modalities: dILB neurons appear to be implicated in the transmission of mechanical pain and chemical itch while dILA neurons seem to function in gating incoming innocuous mechanical information into the dorsal horns. These results begin to establish the functional and circuit differences between the two main neural components of the spinal dorsal horns.



44

P26

Title: Propulsion by coherent advance of actin”: A novel mechanism of actin-based motility drives the growth of axons in vivo in the Drosophila wing

Presenting Author: Edward GinigerCo-Author(s): Akanni Clarke, Hsiao-yu Fang, Phil McQueen, Stephen Wincovitch

Abstract: „Live-imaging of the TSM1 pioneer axon in the developing Drosophila wing reveals a protrusive, non-adherent, filopodial mode of axon growth that is fundamentally different from the adhesive modes that have dominated our thinking about axon extension. We find that the growth cone is not a discrete structure perched at the end of the axon shaft, but rather an emergent property; a statistically-defined zone with a high local actin concentration that drives local filopodial dynamics. We further find that TSM1 extends by a ratchet mechanism whereby a compact actin mass in the leading portion of the axon fluctuates in size longitudinally, but with a bias that favors advancement over retraction. Translocation of the actin into a leading projection causes the axon to grow; translocation into a lateral projection causes the axon to turn. The keys to this mechanism are maintaining cohesion of the leading actin mass and biasing the direction of its fluctuations, and we find that both processes are execu-ted by Abl tyrosine kinase. Overexpressing Abl causes the actin mass in the growth cone to lengthen progressively as the axon extends, until eventually it fragments, causing stalling or misrouting of the axon. Conversely, knock-down of Abl leads to progressive longitudinal collapse of the growth cone, with actin coalescing into small foci and finally contracting into a mass that no longer undergoes fluctuations necessary for ratchet-like motion. Notably, the major mechanism by which Abl deregulation disrupts axon growth is not its effect on the mean values of growth cone parameters, but rather by increa-sing their variance, driving growth cone parameters to outlier values that lie beyond the parameter space compatible with orderly growth. It is these rare outlier events that produce irreversible terminal defects such as growth cone stalling and misrouting. This novel picture of growth cone dynamics reshapes our understanding of the mechanisms underlying axon growth and guidance.



45

P27

Title: Cell-intrinsic regulation of interneuron migration controls cerebral cortex morphogenesis

Presenting Author: Carla Gomes da SilvaCo-Author(s): Elise Peyre, Mohit H. Adhikari, Sylvia Tielens, Sebastian Tan-co, Petra Van Damme, Lorenza Magno, Nathalie Krusy, Maria M. Magiera, Nicoletta Kessaris, Brigitte Malgrange, Annie Andrieux, Carsten Janke, Lau-rent Nguyen

Abstract: Interneurons navigate along multiple tangential paths to settle into appropriate cortical layers. They undergo saltatory migration, which is paced by intermittent nuclear jumps whose regulation relies on interplay between extracellular cues and genetic-encoded information. However, it remains un-clear how cycles of pause and movement are coordinated at the molecular level. Post-translational modification of proteins contributes to cell migration regulation. The present study uncovers that carboxypeptidase 1, which promo-tes posttranslational protein deglutamylation, controls the pausing of migrating cortical interneurons. Moreover, we demonstrate that pausing during migration attenuates movement simultaneity at the population level thereby controlling the flow of interneurons invading the cortex. Interfering with the regulation of pausing not only affects the size of the cortical interneuron cohort but also im-pairs the generation of age-matched projection neurons of the upper layers.



46

P28

Title: Removing the molecular brake on AMPA receptor synaptic accu-mulation leads to learning and memory deficits

Presenting Author: Ines Gonzalez-CalvoCo-Author(s): Iyer K, Khayachi A, Giuliani FA, Vincent J, Albert M, Nadjar Y, Dumoulin A, Triller A, Bessereau JL, Rondi-Reig L, Isope P, Selimi F

Abstract: Complement Control Protein (CCP) modules are emerging as import-ant evolutionarily conserved domains with roles in brain development. One ex-ample is the CCP domain containing protein LEV9 necessary for acetylcholine receptor clustering in C. elegans. Deletion in the gene coding Sushi domain containing protein 4 (SUSD4), a CCP domain containing protein, is associa-ted with autism spectrum disorders or Fryns syndrome in humans. However, the role of SUSD4 in brain development is still unknown. We have shown that Susd4 mRNA is expressed in various regions of the developing brain. Loss of SUSD4 in a constitutive mouse knockout model (Susd4 KO) is associated with motor learning and spatial memory deficits. To understand the cellular function of SUSD4, we analyzed the olivo-cerebellar network, where Susd4 mRNA is ex-pressed in inferior olivary neurons (IONs) and Purkinje cells (PCs). The general architecture of the cerebellum and morphology of PCs is not affected in Susd4 KO mice. Quantitative analysis of synaptic markers reveals no deficits, sugge-sting that synapse formation in PCs is not affected by Susd4 deletion. Using pat-ch-clamp recordings, a significant and transient enhancement in the transmissi-on from the axons of IONs, the climbing fibers (CFs), was detected in Susd4 KO PCs, suggesting an accelerated functional maturation. No significant change in the basal transmission from the parallel fibers (PFs), the axons of the granule cells, was found. However, profound deficits in the long-term plasticity of the PF-PC synapses are induced by SUSD4 deficiency: CF-dependent PF-long-term depression is lost and PF long-term potentiation is facilitated. At the molecular level, these functional changes are accompanied by a specific increase in the synaptic content of GLUR2 receptors, detected by biochemical analyses in ce-rebellar synaptosomes and by immunostaining of brain sections. Affinity puri-fication experiments followed by shotgun proteomics suggest that SUSD4 is a tether for the machinery controlling GLUR2 turnover. Overall, SUSD4 is essenti-al for the fine control of AMPA receptor synaptic accumulation, synapse matura-tion and plasticity, and learning and memory. This study suggests obvious links between SUSD4 deficiency and the etiology of neurodevelopmental disorders.



47

P29

Title: Optical tissue clearing using stabilized organic media allows blea-ching-free deep-tissue imaging of fluorescent whole mouse brain

Presenting Author: Christian HahnCo-Author(s): Klaus Becker, Marko Pende, Saiedeh Saghafi, Inna Sabdyush-eva-Litschauer, Hans-Ulrich Dodt

Abstract: Optical tissue clearing using organic reagents as Dibenzyl Ether (DBE) or BABB (benzyl alcohol and benzyl benzoate 1:2) allows deep-tissue imaging of a wide range of large specimens. Its application is simple and suitable for pa-rallelized experiments. However, peroxides and aldehydes emerge continuous-ly within these organic liquids and cause bleaching of transgenic fluorophores as Enhanced Green-Fluorescent Protein (EGFP), thereby limiting the incuba-tion times. Thus, clearing optimization of fluorescent tissue was finding a tra-de-off in between achieved transparency and signal decay. We found that sta-bilization of DBE or BABB by the addition of a non-toxic anti-oxidant efficiently preserves the fluorescence signal for at least one year. The increased stability enables arbitrary long clearing times and thus better clearing results with high fluorescence signal quality. This allows deep-tissue microscopy of large speci-mens as whole mouse brains with high resolution including dendritic spines.



48

P30

Title: Genetic targeting and functional organization of spinocerebellar tract (CST) interneurons

Presenting Author: Baruch HaimsonCo-Author(s): Yoav Hadas, François Friocourt, Alain Chédotal, Aharon Lev Tov, Avihu Klar

Abstract: Skilled motor performance arises from interactions between efferent neural pathways that induce muscle contraction, and feedback systems that report to the cerebellum and consequently refine movement. Studies in cats have implicated two groups of lumbar-level tract neurons that project to the cerebellum, as a generator of such feedback. DSCT neurons that relay pro-prioceptive information, and VSCT neurons that relay information about internal spinal activity. Despite the existing anatomical knowledge about the two tracts, the lack of genetic targeting tools has hampered dissecting the physiological role of these neurons. Utilizing a newly developed “tool-box” for IN-specific tar-geting and tracking neuronal circuits, that includes neuronal specific enhan-cers, axonal and synaptic reporters, and trans-synaptic viruses, as well as the 3DISCO clearing technique; the functional organization of the chick dorsal in-terneurons dI2 populations was elucidated. Progenitors of dI2 neurons express the Ngn1/2, Lhx1/5, FoxP2 and Foxd3 transcription factors. dI2 neurons re-side at the medial aspect of lamina VII and receive synaptic input from pre-motor neurons. Their axons cross the spinal cord at the segmental level and ascend to the cerebellum where they decussate back ipsilaterally and contact neurons in the granular layer and the medial cerebellar nucleus, at both si-des of the cerebellum. Collateral, lumbar-segmental branches of the ascen-ding dI2 tract, contact the contralateral dI2 and contralateral ipsi-projecting and contralateral-projecting pre-motor neurons. Lumbar level collaterals innervate also wing level pre-motor neurons. We suggest that the dI2 neurons, are tract neurons of the ventral spinocerebellar tract (VSCT), that report the degree of motorneuron‘s activation to the contralateral motor circuitry at the same seg-mental level, between the hind and forelimb and to the cerebellum. The con-sequence of dI2-neuronal silencing on locomotion is currently being tested.



49

P31

Title: Cell-autonomous and non-autonomous mechanisms controlling projection neuron migration

Presenting Author: Andi HansenCo-Author(s): Justine Renno, Carmen Streicher, Lill Andersen, Thomas Rue-licke, Simon Hippenmeyer

Abstract: Concerted radial migration of newly born cortical projection neurons, from their birthplace to their final target lamina, is a key step in the assembly of the cerebral cortex. The cellular and molecular mechanisms regulating the specific sequential steps of radial neuronal migration in vivo are still unclear. Recent evidence suggests that distinct signaling cues act cell-autonomously but differentially at particular steps during the overall migration process. Per-haps unexpectedly, functional MADM (Mosaic Analysis with Double Markers) analyses in comparison to global knockout also indicate a significant degree of cell-non-autonomous and/or community effects in the control of cortical neuron migration. Cell-non-autonomous effects may differentially affect cortical neuron migration in distinct compartments and thus regulate critical steps in the migration process. It is therefore not only essential to determine the nature of the interplay of cell-autonomous and cell-non-autonomous mechanisms but also how they control cortical neuronal migration. Here we established a MADM-based expe-rimental strategy for the analysis of cell-autonomous versus non-autonomous gene function and/or community effects. We pursued subtractive phenotypic analysis of genetic mosaics (wild-type/heterozygote background) with conditio-nal and/or global knockout (mutant background), both coupled with sparse fluo-rescent MADM-labeling of homozygous mutant neurons, to trace the sequential steps of migration in 4D. Using these experimental paradigms we define so far unknown cell-autonomous functions of the p35/CDK5 signaling pathways inter-secting with cell-non-autonomous effects to coordinate radial neuron migration.



50

P32

Title: Alternative polyadenylation of odorant receptor mRNA upon wiring of mouse olfactory sensory neurons

Presenting Author: Yue HeCo-Author(s): Wolfgang Falk, Natja Haag, Martin Bastmeyer, Franco Weth

Abstract: The mammalian primary olfactory system is paradigmatic for its non-topographic, “typographic” axonal wiring pattern. In the mouse, more than 1200 functional odorant receptor (OR) genes are expressed in a monogenic and monoallelic manner by olfactory sensory neurons (OSNs). All axons of OSNs expressing the same type of OR originating from scattered locations of the olfactory epithelium converge stereotypically in one or few of the 1800 glomeruli in the olfactory bulb. Early OR-gene swap experiments suggested that ORs play a critical and instructive role in the OSN axon guidance, the exact mechanism of which, however, has remained controversial. We diffe-rentially screened single-cell cDNA libraries of outgrowing vs. mature OSNs expressing the same OR. We found a profound overrepresentation of a 3’-ex-tended transcript isoform of the analyzed OR exclusively in immature neu-rons. An additional, a short transcript of the same OR, generated by alterna-tive polyadenylation (APA), could be detected in mature OSNs. Meanwhile, we have confirmed the occurrence of APA in multiple other ORs by 3’RACE. Multiplexed quantitative in-situ hybridization and qPCR analysis generally cor-roborated the developmental regulation of these alternatively polyadenylated isoforms with a downregulation of the long in favor of the short isoform upon OSN maturation. RT-PCR analysis of bulbar RNA suggests that the long iso-form might exclusively be located in the axons. We are currently investiga-ting the developmental regulation more thoroughly by using digital PCR and we will address the universality of developmental APA of OR mRNAs through 3’-end RNASeq. Up to this point, our results indicate that the OR, instead of indirectly regulating a downstream guidance apparatus via receptor-specific endogenous activity, as previously suggested, might play a more direct role in the growth cone, necessitating active axonal localization of the OR mRNA.



51

P33

Title: Correlating neuronal birth order with circuit assembly in the Droso-phila optic lobe

Presenting Author: Isabel HolgueraCo-Author(s): Claude Desplan

Abstract: Understanding the molecular mechanisms by which the extensive diversity of neuronal types in the brain assembles to form functional circuits is a central question in neurobiology. The highly stereotyped repetitive columnar and layered organization of Drosophila optic lobe neuropils allows a precise stu-dy of this question. The medulla is the most complex neuropil, being composed of about 100 different neuronal types, and its circuitry is particularly well under-stood. Prior work from our laboratory and others showed that different neuronal types in the medulla are born in a stereotyped temporal manner. Moreover, inter-section between temporal and spatial patterning in the medulla primordium are used to give rise to both uni-columnar and multi-columnar neurons. I will present our on-going strategies to study the correlation between neuronal specification during development and circuit formation in the medulla neuropil in order to iden-tify what are the molecular determinants involved in this fundamental process.



52

P34

Title: Convergent evolution of clustered protocadherins (cPcdhs)

Presenting Author: Zengjin HuangCo-Author(s): Wei Sun , Alexander Meyer, Emre Etlioglu, Daniela Panáková, Wei Chen, Dietmar Schmucker

Abstract: Neuronal receptors exhibiting isoform diversity play important roles in neuronal differentiation and connectivity in vertebrates and invertebrates. In vertebrates, mouse clustered protocadherins (cPcdhs) comprise 58 isoforms with distinct ectodomains derived from three gene clusters (alpha, beta, and gamma). cPcdh isoforms are thought to engage in specific homophilic trans-in-teractions and contribute to neuronal self-recognition and self-avoidance. In addition, cPcdhs are also required for neuronal survival, synaptogenesis, and dendritic branching. However, many key questions regarding cPcdh function have not been addressed for in vivo models. Using Xenopus Tropicalis as a model organism we attempt to address and study the cPcdhs in vivo functions in vertebrate neuronal development, even at a single neuron resolution. We show that X. tropicalis cPcdhs have 96 isoforms derived from three clusters: alpha, gamma1, and gamma2. No distinct Pcdh-beta cluster is present in X. tropicalis. All three clusters are expressed during embryonic development, me-tamorphosis and froglet stages. Highest expression is in the brain, eyes, spi-nal cord and neural crest derived cells. In addition, alpha- and gamma-Pcdh show overlapping, yet also unique expression patterns in different tissue, sug-gesting that different clusters may play common as well as specialized roles. Furthermore, we discovered that alternative splicing of isoforms at the gamma1 cluster generates isoforms that resemble Pcdh-beta isoforms and may play specific roles for the development and brain wiring in the vertebrate. We are currently testing the hypothesis that alternative splicing of Pcdh-gamma1 may represent a form of convergent evolution and may indicate a functional specia-lization of beta-type of cPcdh receptors required in most vertebrate species.



53

P35

Title: The amyloid precursor protein APP collaborates with Contactin2 during dI1 commissural axon guidance

Presenting Author: Laura JabinetCo-Author(s): Tamara Kostovic, Salvatore Pucino, Diego Geering, Esther T. Stoeckli

Abstract: The amyloid precursor protein (APP) is well known to be a key player in the pathophysiology of Alzheimer’s disease by generating A? peptides, the main component of the senile plaques that characterize this disease. Whereas the mechanisms generating A? peptides have been extensively studied, the basic physiological role of APP remains poorly understood. However, APP has been shown to interact with Contactin2 during neurogenesis. Because Contac-tin2 is well known for its role in commissural axon guidance, we tested APP for such a role.To this end, we used in ovo RNAi to investigate whether APP was required for commissural axons to navigate properly across the midline and adopt their rostral trajectory on the controlateral side of the floor plate in the developing chicken spinal cord.Indeed, we found that the downregulation of both APP and Contactin2 impaired commissural axon pathfinding in a si-milar manner, suggesting that APP could act as a guidance cue by interac-ting with Contactin2. With more detailed analyses, we addressed the question whether full-length APP or one of its fragments was required for axon guidance.



54

P36

Title: A drosophila model of injury-induced synaptic plasticity

Presenting Author: Dominik JavorskiCo-Author(s): Thomas Hummel

Abstract: Injuries of the adult nervous system such as peripheral lesions or central focal strokes lead to substantial structural and functional reorganization of neural circuits and boosting these intrinsic neuroplastic processes is critical for functional recovery. Various evidence pointing to compensatory take-over of lost functions not only by adjacent perilesional areas but also an important role of the contralesional hemisphere in recovery, but the cellular resolution of underlying structural changes has been rather limited. Here we are using the adult Drosophila brain as an experimental model to determine the cellular dynamics and molecular mechanisms of injury induced synaptic plasticity. Pre-vious studies have shown that unilateral peripheral lesion within the adult fly olfactory system result in rapid degeneration of sensory afferents but little ch-anges in the overall integrity of the postsynaptic circuit. By employing neuron type specific GRASP technology, we could show that injury-induced loss of sensory input result in distinct synaptic modifications between excitatory pro-jection neurons and inhibitory local interneurons. In addition, theses structural changes in local circuit organization are dependent on contralateral input from isofunctional synaptic regions in the non-affected hemisphere. In ongoing expe-riments we are defining the postlesional temporal dynamics of circuit remode-ling as well as testing candidate regulators of synaptic plasticity in this process.



55

P37

Title: Structure-function relationship of the multifunctional axon gui-dance receptor Robo3

Presenting Author: Alexander Jaworski Co-Author(s): Zachary DeLoughery, Nischal Acharya

Abstract: Axons are guided to their targets by molecular cues, sensed by receptors on the axonal growth cone. Nascent axons can respond to multiple cues simultaneously, integrating guidance signals from various sources. Growth cones are also able to filter guidance information and selectively respond to specific cues during different stages of axon growth. The mechanisms of gui-dance cue integration and filtering are poorly understood.Commissural neurons project axons across the floor plate at the spinal cord ventral midline. Commis-sural axons grow towards the midline in response to the growth-promoting and attractive cue Netrin-1, which signals through the receptor DCC. At the same time, the repulsive cue Nell2 helps guide these axons to the midline by preven-ting them from entering the ventral horn. After midline crossing, floor plate-deri-ved repellants of the Slit family signal through the receptors Robo1 and Robo2 to expel commissural axons from the midline, but Slit repulsion is suppressed before crossing. The divergent Robo family member Robo3 is a receptor for NELL2 but binds neither Netrin-1 nor Slits, and it is critical for commissural axon guidance, as it inhibits Slit repulsion, potentiates Netrin-1 attraction, and medi-ates Nell2 repulsion. Thus, Robo3 integrates the Netrin-1 and Nell2 signals and filters out Slit signaling, and these multiple functions of Robo3 collaborate to gui-de axons towards and across the midline. It has remained unclear how Robo3 is able to execute its three functions in parallel. Here, we study molecular mecha-nisms of Robo3 signaling. We investigated the extracellular interaction between Robo3 and Nell2 and identified the domains in NELL2 and Robo3 that mediate ligand-receptor binding. To elucidate intracellular mechanisms of Robo3 signa-ling, we established an in vitro system for Robo3 structure-function analyses; we use Dunn chambers to study commissural axon turning in response to Netrin-1, Slits, or Nell2, and we test Robo3 constructs lacking defined structural motifs for their ability to restore individual Robo3 functions in Robo3 knockout neu-rons. We used this rescue platform to parse out specific domains of Robo3 that contribute to each of its diverse functions. These studies provide insights into Robo3 signaling and the mechanisms of guidance cue integration and filtering.



56

P38

Title: Dcc is required for somatotopic circuit development and topogno-sis in mice and humans

Presenting Author: Artur KaniaCo-Author(s): Ronan V. da Silva, Helge Johannssen, Matthias Wyss, R. Brian Roome, Farin B. Bourojeni, Nicolas Stifani, Ashley P. L. Marsh, Monique Ryan, Paul J. Lockhart, Richard J. Leventer, Linda J. Richards, Bernard Ro-senblatt, Myriam Srour, Bruno Weber, Hanns Ul

Abstract: Somatotopic organization of neural circuits is proposed to be cri-tical for the spatial perception of sensory stimuli, referred to as topognosis, but causal evidence supporting this claim is sparse. In mammals, nociceptive topognosis has been proposed to be mediated by the lateral spinothalamic pa-thway, formed by spinal commissural neurons that innervate the ventrobasal thalamus. To test whether somatotopy of ascending spinal axons is necessary for pain topognosis, we created a spinal cord-specific knockout mouse line of the Netrin-1 receptor Dcc. Such mice have an increase in ipsilateral spinotha-lamic projections and exhibit bilateral activation of the somatosensory cortex in response to hindpaw noxious stimulation. In addition, these mice displayed mislocalised nocifensive behaviour suggesting loss of topognosis accuracy. Remarkably, we also observed that humans with mirror movements caused by DCC mutations also experience modified topognosis. Altogether, our results de-monstrate that Dcc-mediated spinal midline crossing is critical for spinothalamic somatotopy and provide evidence for its functional relevance for topognosis.



57

P39

Title: Split-Brain in a fly: Developmental mechanism underlying bi-lateral nervous system organisation

Presenting Author: Rashmit KaurCo-Author(s): Sebastian Hoger, Thomas Hummel

Abstract: The two brain hemispheres of bilateral-symmetric nervous systems are highly interconnected by diverse commissural tracts. Famous studies by Roger Sperry showed the importance of bilateral connectivity by performing callosotomy on epileptic patients and demonstrating the asymmetric nature of brain organization and the importance of interhemispheric connection. However, the molecular mechanisms underlying the coordinated development of neural circuits between brain hemispheres are poorly understood. In addition, the sud-den evolutionary appearance of the corpus callosum in placental animals raises the fundamental question of how ipsi-lateral interneurons switch into a commis-sural organization. Using the Drosophila olfactory system, in which sensory neurons directly connect the mirror symmetric olfactory brain regions via a con-tra-lateral connection, we are addressing the cellular and molecular mechanis-ms underlying bi-lateral brain circuit assembly.Here we show that mutations in the cell adhesion molecule Neuroglian result in a specific switch of bi-lateral into uni-lateral olfactory receptor neuron connectivity. Cell-type specific Neuroglian removal via targeted RNAi revealed that in addition to a cell-autonomous func-tion in receptor neurons Neuroglian is also required in a novel class of transient commissural interneurons. Before receptor neuron innervation, commissural in-terneurons not only extend processes within the ipsi-lateral target field but also establish a pioneer commissural tracts. The ipsi-lateral targeting of ingrowing olfactory receptor axons is prevented by Nrg-mediated interneuron adhesion, followed by a contra-lateral guidance, revealing a novel mechanisms to orga-nize the formation of bi-lateral brain circuits. Interestingly, mutations in L1CAM, the Neuroglian homolog in mammals, severely affect corpus callosum develop-ment, indicating evolutionary conserved mechanisms in brain circuit formation.



58

P40

Title: Role of Slit-Robo signaling in the formation of retinotectal layers

Presenting Author: Yvonne KölschCo-Author(s): /

Abstract: Retinal ganglion cells (RGCs) are the sole output of the eye and trans-mit visual information for further processing in the brain. Their main innervation site is the optic tectum, a highly layered structure in the midbrain. In the zebrafi-sh tectum, RGC axons terminate in four innervation domains from superficial to deep: SO, SFGS, SGC and SAC/SPV. Our laboratory has recently shown that Slit signaling through Robo receptors expressed by RGCs is essential for the layer-specific targeting of RGC axons within the tectum (Xiao et al., Cell 2011). Slit1a, provided by tectal cells, appears to act as a classical axon guidance molecule steering axons into the correct tectal layers. However, the slit1a gene is also expressed by a subpopulation of RGCs, suggesting that retina-derived Slit1a shapes axon trajectories. We have set out to disentangle the relative con-tributions of the two Slit1a sources in the formation of visual pathways. First, we investigated the retinotectal projection of a novel slit1a loss-of-function mutant. Whereas, in wildtype larvae, each RGC axon forms a flat terminal arbor, restricted to a single layer, this planar morphology is severely disrupted in slit1a mutants. SO- and SFGS-terminating RGC axons branch aberrantly and frequently cross between layers. Even more dramatically, the deep-projecting subset of RGCs fails to innervate the SGC and SAC/SPV layers altogether. Next, we genera-ted a slit1a:Gal4 BAC transgenic line allowing us to morphologically classify slit1a-expressing RGCs. Intersectional labeling revealed that the majority of this heterogeneous population terminates in SGC and SAC/SPV, which are the layers most affected by slit1a loss of function. Together, these findings prompt the hypothesis that Slit1a may cell-autonomously help to guide RGC axons to the deep tectal layers. Future experiments will employ tissue-specific re-scue and knockout experiments to explore which developmental aspects of the retinotectal projection depend on RGC-derived versus tectum-derived Slit1a.



59

P41

Title: Stage-specific functions of Semaphorin7A during adult hippocam-pal neurogenesis rely on distinct receptors

Presenting Author: Suzanne LemstraCo-Author(s): Bart C. Jongbloets, Roberta Schellino, Mark H. Broekhoven, Jyoti Parkash, Anita J.C.G.M. Hellemons, Tianyi Mao, Paolo Giacobini, Hen-riette van Praag, Silvia De Marchis, Geert M.J. Ramakers, R. Jeroen Paster-kamp

Abstract: The guidance protein Semaphorin7A (Sema7A) is required for the proper development of the immune and nervous systems. Despite strong ex-pression in the mature brain, the role of Sema7A in the adult remains poorly defined. Here we show that Sema7A utilizes different cell surface receptors to control the proliferation and differentiation of neural progenitors in the adult hippocampal dentate gyrus (DG), one of the select regions of the mature brain where neurogenesis occurs. PlexinC1 is selectively expressed in early neu-ral progenitors in the adult mouse DG and mediates the inhibitory effects of Sema7A on progenitor proliferation. Subsequently, during differentiation of adult-born DG granule cells, Sema7A promotes dendrite growth, complexi-ty and spine development through b1-subunit-containing integrin receptors. Our data identify Sema7A as a key regulator of adult hippocampal neuroge-nesis, providing an example of how differential receptor usage spatiotem-porally controls and diversifies the effects of guidance cues in the adult brain.



60

P42

Title: Systematic analysis of human cerebral organoid growth

Presenting Author: Dominik LindenhoferCo-Author(s): Christopher Esk, Thomas Burkard, Jürgen Knoblich

Abstract: Human cerebral organoids are a powerful tool to study brain de-velopment in the context of a human model system. Stem cells exposed to various culture conditions differentiate and generate a variety of brain regi-ons in cerebral organoids, but the contribution of individual stem cells to a hu-man cerebral organoid is unknown. We took two approaches to answer this problem. First, we followed six human stem cell lines with different combina-tion of fluorescent reporters throughout the organoid protocol in microscopy and a quantitative FACS-based approach. Secondly, we labeled each of the 24000 starting stem cells of an organoid with a unique nucleotide barcode in the genomic DNA. This allowed us to follow the relative cell number and contribution of each cell at a given stage of the human cerebral organoid pro-tocol. We show that clonal competition is driving dynamic organoid growth in organoids with mature organoids consisting largely of progeny from a limited number of starting cells. This establishes human organoids as a powerful mo-del to study human in vivo competition and clonal selection. In summary, the-se experiments give insight into how cells compete and evolve during the or-ganoid protocol, providing essential information on organoid growth dynamics.



61

P43

Title: Cooperation between retinal ganglion cells shapes the connectivity of the visual system

Presenting Author: Alice LouailCo-Author(s): Sandrine Couvet, Xavier Nicol

Abstract: A wide range of neuronal connections in the nervous system develop through competitive mechanisms. Pre-synaptic neurons with strong correlated activity with their post-synaptic targets stabilize their connections, in contrast to synapses with uncorrelated pre- and post-synaptic activity. In most connectivity maps including retinal projections, post-synaptic neurons receive input from mul-tiple neurons. The interactions between pre-synaptic terminals and their post-synaptic partners have been extensively studied, however little is known about the interplay between pre-synaptic axons. In the visual system, retinal ganglion cell (RGC) axons from both eyes form a binocular map in their brain targets. This map is initially exuberant before its refinement involving cAMP-dependent competitive mechanisms. We investigated whether cooperation between RGCs is involved to develop precise projection maps. We altered cAMP signaling in sparse RGCs in the retina to investigate the connectivity of their unaffected neighbors. We found that the local and sparse blockade of cAMP signaling mas-sively reduces the projection territory of the manipulated eye, suggesting that neighboring RGCs with unaltered cAMP signals are affected, and that RGC cooperation shapes binocular maps. Using a novel molecular tool enabling to trace unaffected neurons adjacent to RGCs with altered cAMP signaling, we show that blocking cAMP in a subpopulation of RGCs perturbs the projection pattern of their neighbors. To further investigate the mechanisms involved, we monitored the waves of calcium activity propagating throughout the developing retina using a genetically-encoded calcium sensor. These developmental wa-ves are essential for axonal competition during binocular map formation, and are modulated by cAMP. We found that altering cAMP signaling in a few re-tinal neurons was sufficient to perturb calcium waves in the developing retina.



62

P44

Title: Real time large scale in vivo observations reveal intrinsic synchro-ny, plasticity and growth cone dynamics of midline crossing axons during neuronal wiring of the zebrafish spinal cord

Presenting Author: Søren S. L. Andersen

Abstract: How axons are wired in the vertebrate spinal cord has been studied mostly using fixed samples or looking at individually growing axons. Using light-sheet microscopy, early neural development is here followed in vivo in real time at high resolution along several hundred micrometers of the zebrafish spinal cord. The dynamics and time course of cellular development and axonal wiring of interneurons expressing GFP under control of the dmrt3 promotor are analy-zed. Following neurulation, commissural axons are observed crossing the ven-tral floor plate midline perpendicularly at about 20 microns/h and in a manner dependent on the Robo3 but not the EphA4 receptors. Ipsilateral axons extend concurrently, at three to six times higher growth rates and independently of said receptors. At guidance points, commissural axons are seen to decrease their growth rate and cones increase in size. Commissural filopodia appear on the floor plate to interact with the nascent neural network, and thereby trigger immediate plastic and reversible sinusoidal-shaped bending movements of the neighboring commissural shafts. A 3D reconstruction of the 4 dpf spinal cord demonstrates variable dmrt3 cell body position and dimensions, confirmed by single cell Flow-Sight analysis, and also a minor second population of commissurals crossing later and more dorsally. The recordings show the strikingly stereotyped spatio-temporal control that governs axonal wiring of the zebrafish spinal cord. The live observations give renewed perspective on the mechanisms of axonal guidance in the spinal cord that provide for a discussion of the current distinction bet-ween diffusible long-range versus substrate-bound short-range guidance cues.



63

P45

Title: Slit/Robo signals control two guidance steps of oculomotor (III) and trochlear (IV) nerve growth to the eye

Presenting Author: Grant MastickCo-Author(s): Claudia M. Garcia-Pena, G. Eric Robinson, Leonor Nunes, Briel-le Bjorke, Minkyung Kim

Abstract: The alignment and the movement of the eye is controlled by precise innervation of eye muscles by three cranial nerves: oculomotor nerve, troch-lear nerve and abducens nerve; alteration of the connectivity of these nerves can lead to strabismus and eye movement disorders. However, the molecular and cellular mechanisms that guide cranial nerve axons to the eye remains poorly understood. Suggesting that classical guidance cues may be import-ant for cranial nerve guidance, previous results from our lab showed that Slit chemo-repellent proteins and their Robo receptors controlled the contralateral migration of oculomotor neurons. Our current project considers if Slit/Robo si-gnaling controls other steps in the navigation of the oculomotor nerves. To test the potential guidance function of Robos and Slits, we mapped the expression of the proteins, and analyzed Robo1-/- 2-/- and Slit 1-/- 2-/- mutant mice from embryonic stage (E)9.5 to E14.5. We found that Slit1 and 2 are expressed in the ventral areas of the neural tube, and in the eye and surrounding tissue. On the other hand, Robo1 and 2 are expressed by oculomotor axons. In wild type em-bryos, the oculomotor nerve develops in two main stages of navigation. In the first step, from E9.5 to E10.5, axons projected out of the neural tube, forming a pathway from the midbrain to the eye, in a space between the face and the fore-brain, where the axons formed a plexus in contact with a mass of eye muscle precursors. The second step, from E12.5 to 14.5, the oculomotor plexus formed branches that bifurcated to the dorsal and ventral part of the eye. In Slit/Robo mutants, we found alterations in both steps. In the nerve pathway, axons defa-sciculated in early stages of projection to the eye, but in later stages, the axons recovered to align to form a compact single nerve. For the second step, in Slit/Robo mutants, some axons passed the ventral plexus area, while others axons looped or spread out of the plexus area, far away from the eye. We found similar requirements for Slit/Robo signaling in trochlear nerve formation. In wild type embryos, trochlear axons projected out from the hindbrain at 10.5 and contac-ted muscle precursors near the dorsal part of the eye at E12.5. During this na-



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vigation, trochlear axons spread broadly and in parallel, but later fasciculated into a compact nerve. Analyzing Slit/Robo mutants, we found that at E11.5 the trochlear failed to fasciculate and they did not reach the dorsal area of the eye. Instead, axons projected toward the dorsal boundaries of the face and telence-phalon. Our results suggest two different control steps for Slit/Robo signals: one, axon/axon contact during projections to the eye, and second, the plexus area of contact with the muscle precursors. Further investigation is required to uncover how Slit/Robo signals promote fasciculation of the nerves, and how these si-gnals promote the close association of motor axons with muscle precursor cells.



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P46

Title: A multimodal single-cell approach identifies intercellular signaling networks in the developing human neocortex

Presenting Author: Simone MayerCo-Author(s): Jiadong Chen, Dmitry Velmeshev, Ugomma Eze, Beatriz Alvara-do, Mercedes Paredes, Carlos E. Cunha, Arnold R. Kriegstein

Abstract: We have only just begun to understand the diversity of neural proge-nitor cells and the differentiation trajectories of postmitotic cells during human neocortical development. Recent advances in single-cell transcriptomics have identified novel molecular markers defining distinct cell types in the developing and adult neocortex. The combination of single-cell transcriptomics with the phy-siological firing patterns of neurons has revealed a larger diversity of neuronal cell types than previously appreciated. Even though classical synaptic signaling is absent during early stages of brain development, neurotransmitters nonethe-less modulate critical aspects of neural progenitor cell proliferation and differen-tiation, as well as the migration and maturation of newborn neurons. Here we combine single-cell transcriptomics with physiological response characteristics of dissociated cells from the developing human cortex, to achieve a high di-mensional characterization of the diverse cell types. We use a high-throughput method to measure intracellular calcium dynamics in response to a range of neurotransmitters in single cells captured on microfluidic chips. Subsequently, the same single cells are processed for single-cell RNA sequencing. This novel approach enables us to link a cell’s physiological response pattern to its mo-lecular profile. We find that different molecularly identified cell types display dif-ferential responses to a panel of neurotransmitter receptor agonists and thereby uncover how response patterns change with cellular maturation and differentia-tion. Interestingly, progenitor cells in the germinal zone respond preferentially to the application of purinergic and serotonergic agonists, while postmitotic neu-rons in the cortical plate respond to the neurotransmitter receptor agonists that target glutamate and gamma amino butyric acid (GABA) receptors. Moreover, serotonergic receptor activation promotes the proliferation of progenitor cells in the late second trimester. The synthesis of the transcriptomic and physiological fingerprints of a cell allows us to start to decipher the signaling pathways that control the cell biology of different cell types in the developing human neocortex.



66

P47

Title: Developmental coordination during olfactory circuit remodeling in Drosophila

Presenting Author: Oded MayselessCo-Author(s): Dominic S. Berns, Xiaomeng M. Yu, Thomas Riemensperger, Andre Fiala, Oren Schuldiner

Abstract: Developmental neuronal remodeling is crucial for proper wiring of the adult nervous system. While remodeling of individual neuronal populations has been described in both vertebrates and invertebrates, how neuronal circuits remodel, and whether synaptic partners coordinate remodeling, is unknown. Using state of the art genetic tools, and super-resolution imaging, we explored the development of the Drosophila anterior paired lateral (APL) neuron and found that it undergoes stereotypic remodeling during metamorphosis in a si-milar time frame as the mushroom body (MB) ? neurons, with whom they form a functional circuit. By using two binary systems to manipulate two neuronal population simultaneously, we found that inhibiting pruning of MB neurons in-hibited APL remodeling suggesting that circuit remodeling is coordinated. Addi-tionally, the ectopic unpruned ? axons form potentially active connections with the APL neuron as well as dopaminergic and serotonergic neurons, suggesting that inhibiting remodeling of one neuronal type affects the entire micro-circuit.



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P48

Title: Characterization of neuronal circuits for coordinated wing flapping in avian

Presenting Author: Orem Meir, Baruch HaimsonCo-Author(s): Avihu Klar

Abstract: Adaptation to powered flight in birds, that evolved from striding qua-drupedal reptiles, was achieved by the evolution of two main features: mor-phological changes that patterned the wings from limbs, and the transition from alternate gait to synchronous flapping. Comparative genomics analysis revealed that dozens of syntenic gene clusters were deleted in the evolution of birds form reptiles. We hypothesis that the evolvement of wing flapping is a direct consequence of the genome size reduction, either loss of genes or enhancer elements. We found that the gene encoding the repulsive axon gui-dance molecule Ephrin-B3, which serves as a midline barrier for midline axo-nal-crossing of excitatory interneurons in the mouse spinal cord, is missing in chick. Notably, mice null for Ephrin-B3 hop by synchronous gait. Neuronal circuits, at the lumbar (legs) and brachial (wings) levels of the chick spinal cord, were revealed by utilizing targeted expression of reporter genes in speci-fic spinal interneurons and via limb-injected trans-synaptic viruses. We report axonal decussation of excitatory and pre-motor interneurons at the brachial, but not lumbar, dorsal spinal cord. Midline crossing at the lumbar spinal cord is obstructed by an avian-specific ovoid gelatinous mass, termed glycogen body, inserted at the dorsal midline of the lumbar spinal cord. To challenge the role of the loss of Ephrin-B3 in decussation of axons at the brachial level, the mouse Ephrin-B3 was expressed at the dorsal midline of the chick spi-nal cord. Dorsal midline axonal crossing was impeded following Ephrin-B3 expression. Hence, supporting a role for gene-loss in shaping the circuitry at the wing level in avian spinal cord. The consequence of circuity alteration, via ectopic Ephrin-B3 expression, on wing flapping is currently being tested.



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P49

Title: Neuron migration and neurite organization in the Drosophila optic lobe

Presenting Author: Olga MinkinaCo-Author(s): Claude Desplan

Abstract: A key question in developmental neurobiology is how neurons are precisely targeted in the brain to form functional circuits. During Drosophila optic lobe development, two neuroepithelia are progressively converted to neu-roblasts that give rise to 60,000 neurons of more than 100 distinct types that interpret visual information from the retina. Most Drosophila optic lobe neurons do not move far from their place of birth or move after extending processes to the neuropils of the optic lobe. However, two populations of neurons must mig-rate a significant distance from their place of birth through the developing Dro-sophila brain. Once they reach the appropriate location, these two neuron po-pulations send projections that adopt very different morphologies. Notably, both populations of neurons interact with neurons of the same type differently along their length, overlapping each other or avoiding each other depending on their location within the neuropil. I will present strategies to identify the intrinsic and extrinsic signals that direct these neurons to migrate to the appropriate location and to subsequently innervate two neuropils with such diverse morphology.



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P50

Title: A temporal transcriptional switch governs neural stem cell division mode, neuronal numbers and maintenance of terminal differentiation

Presenting Author: Natalia Mora GarcíaCo-Author(s): Carlos Oliva, Alessia Soldano, Mark Fiers, Bassem Hassan

Abstract: Brain disorders caused by imbalance of neuronal numbers, and en-hanced cognitive capacities associated with increase in brain size, suggest the importance of cell number regulation for brain function. In great apes like humans increased neuronal numbers is speculated to derive form a unique subtype of neural stem cells that undergo symmetric self-amplifying divisi-ons, expanding their numbers, before generating neurons. However, there is currently no direct evidence for a causal link. We report the discovery of self-amplifying neural stem cells in Drosophila and show that they arise by a spatio-temporal conversion of self-renewing neural stem cells. This con-version is regulated by a temporal transition in the expression of proneural transcription factors prior to cell division. We demonstrate that the conversi-on from self-renewal to self-amplification is causal to increased neuronal numbers. We further show that the proneural transition acts as a molecular clock controlling both stem cell division mode and neuronal differentiation.



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P51

Title: p27kip1 regulates axonal transport by modulating microtubules acetylation

Presenting Author: Giovanni MorelliCo-Author(s): Aviel Even, Romain Le Bail, Ivan Gladwyn-Ng, Elise Peyre, Bassem Hassan, Jean-Michel Rigo, Juliette Godin, Miguel Weil, Bert Brone, and Laurent Nguyen

Abstract: The cell cycle protein p27kip1 plays functions that go beyond cell-cycle regulation during the formation of the cerebral cortex. This unstruc-tured protein regulates neuronal migration and neurite branching via distinct signaling pathways converging on the actin and microtubule cytoskeletons. p27Kip1 is a microtubule (MT)-associated protein (MAP) that decorates the axons of projection neurons and as such may regulate the transport of orga-nelles and synaptic vesicles. Axonal transport is essential for the maturati-on of neurons but also for the establishment of neuronal connectivity though synapse formation and maintenance. The present work demonstrates that p27Kip1 controls axonal transport of organelles and cargos in mouse pro-jection neurons in microfluidic devices. Moreover, knockdown of Dacapo, the p27kip1ortholog in Drosophila melanogaster, disrupts axonal transport in vivo, leading to the reduction of locomotory activities in both 3rd instar lar-va and adult flies. At the molecular level, we found that p27Kip1 stabilizes the ? tubulin acetyltransferase ATAT1, thereby promoting the acetylation of MTs, a posttranslational modification required for proper axonal transport.



71

P52

Title: Zic2 induces axon steering at the midline by increasing the levels of ß-catenin independently of the canonical Wnt signaling

Presenting Author: Cruz MorenillaCo-Author(s): Jose Lopez-Atalaya, Angel Barco, Eloísa Herrera

Abstract: In species with bilateral symmetry neural circuits containing ipsilateral and contralateral tracts distribute sensory information coming from both sides of the body to integrate it in the main processing centers of the brain in order to generate coordinated motor responses. The transcription factor Zic2 specifies axonal ipsilaterality in at least two different types of neurons, retinal ganglion cells (RGCs) and spinal neurons but through the expression of two different tyrosine-kinase receptors, EphB1 in the visual system and, EphA4 in the spinal cord. Here, we aimed to further identify Zic2 targets in an unbiased manner and explore to what extent this transcription factor shows a similar binding profile in different neural types. Our genomic screens revealed that, with few exceptions, Zic2 binds to the same genomic regions in both types of differentiated neurons. Furthermore, Gene Ontology (GO) analyses evidenced that Zic2 binds to the promoter region of many genes involved in the Wnt-signalling pathway. Con-sistent with this observation, an unbiased RNA-Seq based screen designed to search for Zic2 targets, points at Zic2 as a negative regulator of many genes functioning in the canonical Wnt signaling pathway. However, functional expe-riments revealed that ectopic expression of Zic2 in RGC axons enhances the accumulation of ß-catenin, the main read out of the Wnt-signalling pathway. In utero electroporation of a non-degradable form of ß-catenin reproduces the axon midline avoidance phenotype observed after ectopic expression of Zic2 in RGCs and a similar axonal phenotype is observed after electroporati-on of a mutant form of ß-catenin lacking the transactivation domain. All these results together suggest that Zic2 blocks the canonical Wnt signalling but in-duces accumulation of ß-catenin at the axons to promote midline repulsion.



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P53

Title: Engineered cerebral organoids (enCORs) model effects of fetal alcohol exposure on tissue architecture

Presenting Author: Alexander PhillipsCo-Author(s): E. Hilary Gustafson, Simone Wolfinger, Juergen A. Knoblich, Madeline A. Lancaster

Abstract: The combination of engineering and self-organization in brain organoids allows for the generation of more homogeneous tissues while maintaining com-plexity and advanced tissue architecture. Engineered cerebral organoids (en-CORs) provide the first in vitro system for modelling the distinctive radial organi-zation of cortical neurons and allow for the study of neuronal migration. Here, we demonstrate that teratogenic effects of fetal exposure to high doses of ethanol can be recapitulated in enCOR organoids. Our results suggest that defects in cortical plate formation resulting from competition with retinol metabolism may be responsible for the neuronal migration deficits in fetal alcohol syndrome. These data demonstrate the utility of engineered cerebral organoids for modelling ef-fects of teratogenic compounds and investigating the biochemical mechanism.



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P54

Title: Live monitoring reveals spatial and temporal codes of guidance receptor dynamics during commissural axon navigation

Presenting Author: Aurora PignataCo-Author(s): Hugo Ducuing, Karine Kindbeiter, Muriel Bozon, Leila Boubakar, Julien Falk, Olivier Thoumine, Valérie Castellani

Abstract: During embryonic development, commissural axons navigate through the ventral midline, crossing from one side of the CNS to the other one at specific time points and positions. Various ligand/receptors couples mediate the repul-sive cascades necessary to induce proper guidance responses of commissural growth cones. How is achieved the functional specificity of these repulsive cas-cades suggested by different outcome of their invalidation in mouse models, still remains unknown.We hypothesized that regulation of the spatial and temporal dynamics of guidance receptors at the growth cone surface might be crucial to the setting of the guidance sequences orchestrating commissural axon navigation from the pre-crossing to the post-crossing steps. We developed a set up based on time-lapse imaging of open spinal cords, to monitor the dynamics of guidance receptors in axons experiencing native guidance decisions across the midline. To monitor their cell surface sorting, receptors were fused to the pH-sensitive GFP, pHluo, whose fluorescence at neutral pH reports membrane protein pools (Na-wabi et al, 2010; Delloye-Bourgeois et al, 2014), and were expressed in commis-sural neurons through in ovo electroporation. Live imaging and super-resolution microscopy revealed striking differences in the temporal dynamics of Robo1, Robo2 and PlexinA1, the receptors known to mediate the responsiveness to the major midline repellents referenced in vertebrates: Slit-Ns, Slit-Cs and Sema-phorin3B. Moreover, we found that PlexinA1 and Robo1 are sorted in distinct subdomains of commissural growth cones navigating the floor plate, thus also revealing spatial specificities. In contrast, we found that Robo2 is surprisingly not sorted during the crossing but long after, in the post-crossing compartment at the interface between the ventral and the lateral funiculi. We also found that the surface sorting of Robo2 is controlled by motoneuron-released cues, and must be achieved at proper timing. Thus, our study reveals that guidance receptors for midline repellents have highly specific spatial and temporal dynamics, and uncovers an additional intermediate target for commissural axons, triggering changes of receptor equipment for proper post-crossing pathway selection.



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P55

Title: Development of retinotopy in the fly motion detection circuit

Presenting Author: Filipe Pinto-TeixeiraCo-Author(s): Koo, C., Del-Valle-Rodriguez, A., Desplan, C.

Abstract: The activity of a neuronal network relies on precise connectivity bet-ween neurons. Understanding how a relatively small number of genes produce the complexity of brain wiring during development is one of the greatest challen-ges in neurobiology. A conspicuous example of such complex, yet approacha-ble, organization is found in the Drosophila optic lobe. The signal from each of the 800 ommatidia (the unit eye) is processed in the optic lobe neuropiles, organized in retinotopic columns, each processing the information of one point in visual space. The direction-selective T4 and T5 neurons are a well-studied class of neurons whose activity relies on such retinotopic organization. Within each column, there are four subtypes of T4 and of T5 neurons that receive their inputs in the medulla (T4) or lobula (T5) neuropiles. Each T4 and T5 subtype responds to one direction of local motion along each of the four cardinal direc-tions (vertical up-down and down-up, and horizontal front-back and back-front). We used clonal analysis, genetic perturbations and live imaging to investigate how the identity of the four subtypes of T4 and of T5 neurons is specified and how their retinotopic organization is established during development. We show that T4 and T5 neurons are produced by a previously uncharacterized type of neurogenesis: Vertical and horizontal motion sensitive T4/T5 neurons, each originate from two distinct populations of neuroprogenitors. Each neuroproge-nitor divides once in an asymmetric Notch-dependent manner to produce two distinct intermediate progenitors (GMCs). Each GMC divides once, also in a Notch-dependent manner, producing sibling T4 (NotchOFF) and T5 (NotchON) neurons of the same subtype. Finally we show that T4 and T5 sibling cells project retinotopically in the neuropiles and thus process information from the same point in the visual space. We propose a model in which retinotopy results from patterns established by neuronal birth order. This illustrates how a com-plex neuronal organization can be implemented by simple developmental rules.



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P56

Title: “What big eyes you have”: a multiscale analysis of the logic and mechanisms of natural variation in eye size

Presenting Author: Ariane RamaekersCo-Author(s): Simon Weinberger, Annelies Claeys, Jiekun Jan, Martin Kapun, Reinhard Wolf, Thomas Flatt, Erich Buchner, Bassem A. Hassan

Abstract: The variation of sensory organ or brain area size observed in nature – such as eye size differences between closely-related diurnal and nocturnal species, expansion of brain nuclei involved in vocalization in songbirds and of pri-mate cortex– demonstrates that nervous system development can successfully accommodate quantitative variation. In this work, we investigated the mecha-nisms of developmental variation in the nervous system using natural variation of fruit fly compound eye size as a model amenable to a combination of compa-rative and molecular genetics approaches. We found that variation of Drosophi-la compound eye size, that we associated with variation in visual acuity, derives from changes in the proportion of the fruit fly head primordium directed towards eye versus non-eye fate. Interestingly, these changes in patterning underlie eye size variation between two distant Drosophila species as well as between two D. melanogaster laboratory strains, suggesting that evolution is biased towards specific “variation-prone” processes. We identified a naturally occurring sing-le nucleotide polymorphism (SNP) present in most natural fruit fly populations across the world in the non-coding sequence of the highly-conserved regulator of eye development eyeless (Pax6). Using CRISPR/Cas9 genome editing, we demonstrated that the eyeless SNP is causal to eye size variation. Importantly, this SNP is located in a predicted binding site for eyeless repressor Cut and affects the temporal dynamics of eyeless enhancer activity. This suggests a mo-del by which differential binding of Cut to the eyeless enhancer, caused by the SNP, results in different dynamics of eye fate specification, ultimately leading to eye size variation. Thus, by combining comparative and molecular genetics approaches, this multi-scale study advances our understanding of the develop-mental mechanisms of natural morphological variation in the nervous system.



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P57

Title: The absence of sensory axon bifurcation affects sensory informa-tion processing and termination fields of afferents in the spinal cord

Presenting Author: Fritz G. RathjenCo-Author(s): Philip Tröster, Julia Haseleu, Jonas Petersen, Oliver Drees, Achim Schmidtko, Frederick Schwaller, Gary R. Lewin, Gohar Ter-Avetisya-n,York Winter, Stefanie Peters, Susanne Feil, Robert Feil, Hannes Schmidt

Abstract: A cGMP signaling cascade composed of C-type natriuretic peptide, the guanylate cyclase receptor Npr2 and cGMP-dependent protein kinase I (cGKI) controls the bifurcation of sensory axons upon entering the spinal cord during embryonic development. Here we generated conditional mouse mutants of Npr2 and cGKI (Npr2fl/fl;Wnt1Cre and cGKIKO/fl;Wnt1Cre) lacking sensory axon bifurcation in the absence of additional phenotypes observed in global knockout mice. These mutants allowed us to clarify the functional consequences of impaired axon bifurcation for sensory processing in adulthood. Behavioral testing of both sexes indicated that noxious heat sensation and nociception in-duced by chemical irritants are impaired in these mutants, whereas responses to mechanical stimulation and motor coordination are not affected in conditio-nal mouse mutants. Recordings from C-fiber nociceptors in the hind limb skin showed that Npr2 function was not required to maintain normal heat sensitivity of peripheral nociceptors. Thus the altered behavioral responses to noxious heat found in Npr2fl/fl;Wnt1Cre mice is not due to an impaired C-fiber function. Cholera toxin labeling in digits of the hind paw demonstrated that in conditional Npr2 mouse mutants the shape of termination fields of primary afferents from the skin is quantitatively and qualitatively altered. Overall, these data indicate that pain processing is more sensitive to a reduced convergence due to impai-red bifurcation than sensory systems implicated in perception and control of balance and coordination. Furthermore, our mouse data might provide grounds for neurological testing of human patients with mutations in the Npr2 gene.



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P58

Title: Plexin-A1 and Semaphorin-6D are involved in retinal axon targeting

Presenting Author: Alexandra RebsamCo-Author(s): Delphine Prieur, Cedric Francius, Patricia Gaspar, Carol A. Ma-son

Abstract: Most axons regroup into nerve tracts as they are guided towards their target and must defasciculate and exit this tract in order to innervate their speci-fic targets. However, how axon fasciculation and target innervation are regula-ted is still unclear. Retinal axons from the same (ipsilateral) and the opposite (contralateral) eyes gather in the optic tract and then innervate separate terri-tories in the dorso-lateral geniculate nucleus (dLGN), forming an eye-specific map. We investigated the role of the guidance receptor Plexin-A1 and its li-gand Semaphorin-6D (Sema6D) in these targeting processes. After anterogra-de tracing, Plexin-A1 -/- or Sema6D -/- mice present ectopic retinal projections in the dLGN, without alterations in topographic mapping. A 3DISCO clearing of Sema6D -/- mouse brains allowed 3D visualization and revealed that ipsilateral projections extend and form a new ipsilateral territory on the other side of the optic tract. A similar phenotype is observed in Sema6D +/- Plexin-A1 +/- mice but not in single heterozygotes, indicating that Sema6D and Plexin-A1 interact together for the appropriate target innervation by retinal axons. Both Plexin-A1 and Sema6D are expressed in retinal ganglion cells and dLGN during postnatal development. To determine where the expression of Plexin-A1 and Sema6D is required, we used in utero electroporation of Sema6D-shRNA or Plexin-A1-shR-NA to knock-down their retinal expression before target innervation. Mice elec-troporated with Sema6D-shRNA or Plexin-A1-shRNA present similar targeting defects as Sema6D -/- and Plexin-A1 -/- mice in the dLGN and we found non-cell autonomous effects for both of them. Thus, we showed that the expression of Sema6D and Plexin-A1 in the retina is essential for retinal axonal targeting.



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P59

Title: Neuronal diversity of the hypothalamus: new subtype of hypothala-mic dopamine neurons

Presenting Author: Roman RomanovCo-Author(s): Zeisel A., Bakker J., Tomer R., Deisseroth K., Hökfelt T., Bock C., Linnarsson S., Horvath T.L., Harkany T

Abstract: The mammalian hypothalamus contains a kaleidoscope of cellular modalities, producing the highest diversity of neurons in the brain. Investigators relied on candidate tools to correlate behavioral, endocrine or gender traits with hypothalamic neuronal identity. Since as few as some hundreds of neurosecreto-ry/neuropeptidergic neurons can define critical endocrine output, it is likely that additional neuronal subtypes still exist in the mammalian hypothalamus. The conglomerate of nuclei encompassing the paraventricular and arcuate hypo-thalamic areas integrates metabolic and stress circuitries with their complex network design allowing metabolically controlled neurotransmitter-neuropepti-de co-release. We used RNA-seq on > 3,000 dissociated cells of the hypot-halamus and a divisive biclustering method (BackSpinV2 algorithm) to reveal neuronal types and circuit modalities in this brain region. We distinguished 62 molecularly segregated neuronal subtypes in the hypothalamus, which produce dopaminergic, GABAergic or glutamatergic codes for synaptic neurotransmissi-on. By combining our RNA-seq data with in situ hybridization-derived positional information, we revealed novel peptidergic neuronal subtypes. Next, we identi-fied dopamine neurons that uniquely coexpress the Onecut3 and Nmur2 genes, and placed these in the periventricular nucleus with many synaptic afferents arising from neuromedin S+ neurons of the suprachiasmatic nucleus. These neuroendocrine dopamine cells may contribute to the dopaminergic inhibition of prolactin secretion diurnally, as their neuromedin S+ inputs originate from neu-rons expressing Per2 and Per3 and their tyrosine hydroxylase phosphorylation is regulated in a circadian fashion. Overall, our catalog of neuronal subclas-ses provides new understanding of hypothalamic organization and function.



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P60

Title: Studying axon guidance and neuronal migration with selective interference of second messenger function in vivo

Presenting Author: Oriol RosCo-Author(s): Sandrine Couvet, Yvrick Zagar, Karine Loulier, Solène Ribes, Xavier Nicol

Abstract: Second messengers are mid-point relays in signaling cascades go-verning a wide range of cellular functions. Their precise control is required at several steps leading to the sound connectivity of the nervous system. How neurons are able to discriminate between second messenger signals arising from different stimuli is unknown. Thus, being able to interfere with transient or local changes in second messenger concentration in a developing neuron is critical to unveil the developmental mechanisms wiring the brain.We have developed “cGMP Sponge” and “Calcium Sponge”, a pair of genetically-en-coded buffers that alter physiological changes in the concentration of cGMP and calcium respectively. These tools enable disrupting signaling cascades with cellular and subcellular resolution and might shed light on how neurons percei-ve the significance of second messenger variations in response to guidance stimuli. They provide an approach to investigate how nervous networks arise.We provide evidence that cGMP Sponge and Calcium Sponge, both in soluble form or targeted to the lipid raft or non-lipid raft compartments of the plasma membrane, are able to buffer changes in the respective second messenger concentration. Using in utero electroporation we show that calcium and cGMP signaling are crucial for the correct migration and placement of newly genera-ted cortical neurons. We further show how second messenger signaling in lipid rafts is required for the response of retinal ganglion cell axons to guidance cues.



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P61

Title: Slitrk2 and Slitrk5 differentially control excitatory and inhibitory sy-napse formation on dopaminergic neurons and hyperactivity behaviour

Presenting Author: Charleen SalesseCo-Author(s): Julien Charest, Hélène Doucet-Beaupré, Paul De Koninck, Martin Lévesque

Abstract: Midbrain dopaminergic (mDA) neurons are critically involved in va-rious key functions of the brain, including voluntary movement, reward, atten-tion, and learning. Dopaminergic circuitry dysfunctions are linked to the de-velopment of neuropsychiatric disorders, including attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD) and OCD-like disor-ders, such as Tourette’s syndrome (TS). The LIM-homeodomain transcriptional factors Lmx1a and Lmx1b are early determinants of the dopaminergic fate and are essential for each step of mDA progenitor differentiation. We have previous-ly demonstrated that Lmx1a/b cKO mice show ADHD and OCD like behaviour. We found that the loss of function of Lmx1a/b reduced dendritic morphology and frequency of spontaneous miniature excitatory postsynaptic currents (mEP-SCs) in mDA neurons. Gene expression profiling in Lmx1a/b cKO mice revea-led that Lmx1a/b controls the expression of Slitrk2 and Slitrk5, two members of the Slit and Trk-like (Slitrk) protein family. Gain and loss of function of Slitrk2/5 in mDA neuron cultures showed that Slitrk2 positively regulates and Slitrk5 ne-gatively regulate dendritic growth. More specifically, gain and loss of function of Slitrk2 induced a change in the density of excitatory synaptic puncta (PSD95 and VGLUT). Accordingly, we observed a reduction in the frequency of mEP-SCs after Slitrk2 knockdown and an increase when Slitrk2 is overexpressed. These data suggest a role for Slitrk2 in the formation of functional excitatory synapses. Inversely, gain and loss of function of Slitrk5 induced a modification in the density of inhibitory synaptic puncta (gephyrin and VGAT). We also ob-served a reduction in the frequency of mIPSCs after Slitrk5 knockdown and an increase when Slitrk5 is overexpressed. These data suggest a role for Slitrk5 in the formation of functional inhibitory synapses. We also investigated the con-sequences on behaviour of Slitrk2 and Slitrk5 reduced expression in mDA neu-rons. Mice, in which Slitrk2 was knocked-down in the VTA, display significant change in locomotor activity and show ADHD and OCD-like behaviour. Inver-sely, mice with reduced expression of Slitrk5 exhibit lower activity. We hypothe-



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size that these behavioural changes are caused by a change in mDA neuron firing activity. Chronic inhibition of mDA neurons during postnatal development using a pharmacogenetic approach induced ADHD and OCD-like behaviour and mimic some aspects of the Lmx1a/b cKO mice. Altogether, our results indicate that Lmx1a/b and Slitrk2/5 are key players of mDA neuron development and sy-napse formation, which may have an impact on ADHD and OCD-like disorders.



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P62

Title: Neuron Navigator-1 is an actin-binding microtubule plus-end tracking protein (+TIP) that controls the cyoskeletal dynamics in the neuronal growth cone

Presenting Author: Carlos Sanchez-HuertasCo-Author(s): Amandine Falco, Jeffrey van Haren, Ralph Sanders, Niels Gal-jart, Jerome Boudeau, Anne Debant

Abstract: Making the proper nerve connections is essential for brain develop-ment and function. The neuronal growth cone (GC) is employed by neurons to find their appropriate targets, and this requires a delicate coordination bet-ween the microtubule (MT) and actin networks within it. The MT plus-end dy-namic instability is tightly controlled by microtubule plus-end tracking proteins (+TIPs). Some +TIPs also interact with F-actin or with actin-binding proteins in the peripheral region of the GC to promote selective stabilization of the plus-end or to guide the MTs along F-actin bundles. Reciprocally, some +TIPs can serve as modulators of actin filament nucleation and organization. These cy-toskeletal cross-talk mechanisms determine the axon navigation in response to guidance cues, and they are far from being fully elucidated. The Neuron Navigator-1 (NAV1) is a +TIP enriched in the developing nervous system, and it,has recently been assigned a role in regulating the functions of the Rho-GT-Pases activator Trio in neurite extension. Here we show that NAV1 is an EB-dependent +TIP accumulating in the neurite tips of immature cortical neu-rons, and more broadly, wherever F-actin accumulates in the cell. In neurons, NAV1 shows the typical +TIP localisation pattern and behaviour exclusively in the F-actin rich regions, suggesting that it could be an actin cytoskeleton interactor. Consistenty, we have found that NAV1 binds directly to F-actin in vitro. NAV1 depletion in cultured immature cortical neurons led to a reduction in the number of MTs reaching the periphery of the growth cone, an increa-se in the size of the growth cones and in the number of filopodia per growth cone, together with a faster rate of filopodia extension. In addition, FRAP ana-lysis revealed a more dynamic actin filament turnover within the growth cone of NAV1-depleted neurons. Consistently, we found that the absence of NAV1 increases the erratic motion of the growth cones, with more frequent chan-ges of direction during navigation and a faster outgrowth. Altogether, our re-sults show that NAV1 is a new F-actin-binding +TIP that facilitates MT invasion and represses F-actin remodeling in the growth cones. We propose that NAV1 has a role in coupling the MT and actin networks to coordinate their dyna-mics, and is thereby a key controller of growth cone steering and protrusion.



83

P63

Title: Signaling balance of Semaphorins and Neurotrophins controls the sexually dimorphic innervation of the mammary gland

Presenting Author: Hadas Sar ShalomCo-Author(s): Ron Goldner, Avraham Yaron

Abstract: The innervation of peripheral targets is largely regulated by the levels of target-derived trophic factors. But whether additional target-derived factors act in concert with these trophic factors and their identity is largely unknown. Sensory innervation of the mammary gland is controlled by BDNF signaling ear-ly during development. Afterward, these axons are pruned only in males due to sequestering of BDNF by expression of the truncated form of TrkB. In search for cues that control the innervation together with BDNF we have found a specific expression of the membrane bound repulsive molecule Sema6A and members of the class three secreted Semaphorins in the gland’s epithelial cells. Moreo-ver, these class three Semaphorins and Sema6A induced growth cone collapse of BDNF responsive sensory neurons, in a Plexin-A4 dependent manner. Abla-tion of Sema6A or the Semaphorins receptor Plexin-A4, caused developmental hyperinnervation of the gland by sensory axons, which was balanced by genetic reduction in the levels of BDNF. Strikingly, in males, PlexinA4 ablation caused a strong delay in the pruning of the fibers innervating the gland independently of the initial levels of innervation. Overall, our studies show that developmental innervation of the mammary gland is regulated by a balance between BDNF, which promotes the initial ingrowth of the sensory fibers, and the Plexin-A4 signaling pathway that restricts the innervation. In males, upon inhibition of the BDNF-TrkB signaling Plexin-A4 signaling is critical to promote axonal pruning.



84

P64

Title: GFRa1-dependent survival of cerebellar molecular layer interneu-rons is important for motor learning

Presenting Author: Maria Christina SergakiCo-Author(s): Juan Carlos López-Ramos , Stefanos Stagkourakis , Agnès Gruart, Christian Broberger, José María Delgado-García, Carlos F. Ibáñez

Abstract: The formation of functional neuronal circuits depends on proper de-velopmental processes that ensure sufficient neuron number and their correct positioning within their target layers. In the cerebellum, gabaergic molecular layer interneurons (MLIs) provide the major source of inhibition to Purkinje cells (PCs), the sole output cell of the cerebellar cortex. However, the signals controlling the survival of MLIs are unknown, and direct evidence for the requi-rement of a full complement of MLIs for normal cerebellar circuit function and motor learning has been lacking. Here we show that PCs express the neurot-rophic factor GDNF during MLI development and survival of MLIs depends on the GDNF receptors GFR?1 and RET. Conditional deletion of either receptor leads to the loss of a quarter of MLIs, resulting in reduced synaptic inhibition of PCs, increased PC firing frequency and abnormal acquisition of eyeblink conditioned responses and deficits in vestibulo-ocular reflex performance. Interestingly loss of GFR?1 or RET does not affect the overall motor activity or coordination. These results identify an endogenous survival mechanism for MLIs and reveal the selective requirement of MLIs in the control of cerebellar-dependent motor learning.



85

P65

Title: Guidance of thalamic axons in the subpallium regulates cortical arealization

Presenting Author: Alexander Sinclair-WilsonCo-Author(s): Proville, R., Spolidoro, M., Lena, C., Grosschedl, R., Garel, S., Lokmane, L.

Abstract: The mammalian neocortex is organized in its tangential dimension into discrete and functionally specialized areas, each characterized by its unique pattern of gene expression, cytoarchitecture and connectivity. The formation of the functional cortical map involves a sequential combination of i) morphogene-tic signals derived from within the cortex, and ii) extrinsic information, including signals from thalamic axons. The precise nature of the instructive relationship between incoming thalamocortical axons (TCAs) and the development of the arealised cortex, however, remains to be established. During embryogenesis, thalamocortical axons (TCAs) are organized in the subpallium as topographic projections and follow distinct, stereotypical paths towards different target regi-ons. Recent research from our lab has revealed that growing TCAs are initially misrouted in the subpallium of Dlx5/6::cre;Ebf1fl/- mutant mice but then subs-equently rerouted within the postnatal cortex, ultimately innervating the correct target areas. Here we combine this Dlx5/6::cre;Ebf1fl/- model with axonal tracing techniques, gene expression analysis and behavioural testing to examine the role of intermediate TCA guidance defects on cortical area development and function. We show that despite the rewiring of misguided TCAs, the intermedia-te trajectory of TCAs in the mutant subpallium significantly influences cortical area development and function. This research provides important new insights into the extrinsic, thalamic input-mediated control of cortical map formation.



86

P66

Title: Afadin disrupts central canal formation and gait selection

Presenting Author: Sophie SkarlatouCo-Author(s): Niccolò Zampieri

Abstract: Afadin is an actin-binding protein that plays important roles in cell-cell recognition by controlling the activities of the nectin and cadherin families of cell adhesive molecules (Takai et al., 2008). Afadin signaling participates in many morphogenetic processes during development (Takai et al., 2008, Riki-take et al, 2012). In the nervous system it has been implicated in the control of synapse formation and neuronal migration (Mizoguchi et al., 2002, Beaudoin et al., 2012, Gil-Sanz et al., 2013). Nectins and afadin expression patterns in the spinal cord are suggestive of possible functions for these proteins in the development of spinal sensory-motor circuits, however, their contributions re-main largely unexplored. To address a potential role for afadin in the assembly and function of spinal motor circuits, we generated a conditional knock-out mouse in which afadin has been selectively eliminated from motor neurons. Afadin inactivation results in a striking locomotor phenotype: a switch from left-right alternation to a synchronous movement of paired limbs. In order to start gaining insights into the possible mechanisms underlying this phenotype, we analyzed spinal motor circuits development in afadin mutants and observed a defect in central canal formation that enables aberrant premotor connectivity.



87

P67

Title: Astrocytic neuroligins control astrocyte neuropil infiltration and synaptic connectivity

Presenting Author: Jeff StogsdillCo-Author(s): Juan Ramirez, Yong-Ho Kim, Di Liu, Katherine Baldwin, Eray Enustun, Tiffany Ejikeme, Ru-Rong Ji, Cagla Eroglu

Abstract: Astrocytes are morphologically complex cells of the brain that perform critical central nervous system functions. Fine cellular processes of astrocytes penetrate the neuropil, thereby maintaining synaptic homeostasis and modulate synapse numbers and strength. The cellular and molecular mechanisms that control neuropil infiltration and overall cellular morphogenesis of astrocytes is lacking. Furthermore, it is unclear how the morphological development of as-trocytes affects synaptic connectivity. Here, we uncover that cortical astrocyte morphogenesis is dependent on direct contact with neuronal processes. Unex-pectedly, astrocyte morphology and neuropil infiltration is dependent upon the expression of the neuroligin (NL) family of cell adhesion proteins NL1, NL2, and NL3 within astrocytes. Transcellular interactions between astrocytic NLs and their well-known neuronal binding partner neurexins (Nrx) regulate the morphology of astrocytes. To gain insight into the link between astrocyte neuropil infiltration and synaptic connectivity, we deleted NL2 specifically in astrocytes and quantified synapse numbers and measured synaptic function. Surprisingly, deletion of NL2 in cortical astrocytes impairs excitatory synaptic connectivity, while inhibitory sy-naptic function is enhanced. Our findings uncover a novel mechanism of action of NLs in astrocytes and reveal a connection between astrocyte morphology and synapse formation. Loss-of-function mutations in NLs, including NL2 are implica-ted in human cognitive disorders such as autism and schizophrenia. Therefore, understanding the distinct roles of these cell adhesion molecules in astrocytes and neurons is fundamental to unraveling their mechanisms of neural pathology.



88

P68

Title: Collaterals patterning of dorsal spinal interneurons instructed by motor neurons- derived repulsive and V0-derived attractive cues

Presenting Author: Reut SudakevitzCo-Author(s): Lilach Dvir, Baruch Haimson, Terry Levkvisj, Cole Bendor, Avihu Klar

Abstract: Spinal dI2 are spinal tract interneurons that integrate and relay net-work activity of multiple rostral/caudal levels to brain centers. Utilizing enhancer intersection and spatially-restricted electroporation in the chick spinal cord, the axonal patterning of dI2, was decoded. The axons of dI2 are projected com-missurally. After crossing the floor plate (FP), axons are deflected laterally in the white matter, and elongate longitudinally at the lateral funiculus. At E9, col-laterals branches sprout and invade the gray matter at two locations: between the FP and the motor neurons zone (MNz), and dorsally to MNz, while avoiding the MNz. We hypothesized that the ventral spinal cell-constituent instruct dI2 branching pattern via repulsion from MNz and attraction to its flanking zones. To test whether MN repels dI2 collaterals, unilateral labelling of dI2 neurons and axons was attained together with manipulation of MN at the contralateral side. Ectopic MN, induced by ectopic expression of Isl1+Lhx3, reduced dI2’s colla-terals, while reduction of MN, achieved by limb removal, resulted in invasion of collaterals to the ventrolateral spinal cord – the region of the depleted MN. To test whether attractive cue direct collaterals patterning, we initially interrogated potential cell-substrates. V0 and V1 are the largest ventral interneuron popula-tions. Co-labelling of dI2 axons and the contralateral V0 and V1 demonstrates that dI2 axons overlap with V0 and V1 cell bodies, axons and dendrites. To gain insight to the possible role of V0 and V1 in attraction of dI2s’ collateral, they were induced ectopically by ectopic expression of Dbx1 or Prdm12, respec-tively. Induction of ectopic V0 neurons elevated the amount of collaterals. Enor-mously projecting collaterals overlap with ectopic V0. Ectopic V1 did not alter the projection of dI2’s collaterals. Hence, the pattern of dI2s’ collateral is instruc-ted by attractive and repulsive cure emanating from V0 and MN, respectively.



89

P69

Title: Meninges-derived cues control axon guidance

Presenting Author: Tracey SuterCo-Author(s): Zachary J. DeLoughery, Alexander Jaworski

Abstract: During nervous system development, growing axons are guided to their targets by a combination of attractive and repulsive cues. These cues can be presented as gradients of diffusible factors or as cell surface- and extracel-lular matrix-attached molecules, and they are often produced by guidepost cells, which are positioned at intermediate targets or boundaries of the axonal trajectory and serve as choice points The full repertoire of axon guidance cues and receptors and the identity of the tissues producing these cues remain to be elucidated. The meninges are connective tissue layers enveloping the verte-brate brain and spinal cord that serve to protect the central nervous system (CNS). The meninges also instruct nervous system development by regulating the generation and migration of neural progenitors, but it has not been deter-mined whether they help guide axons to their targets. Here, we investigate a possible role for the meninges in neuronal wiring. Using mouse neural tissue explants, we show that developing spinal cord meninges produce secreted attractive and repulsive cues that can guide multiple types of axons in vitro. We find that motor and sensory neurons, which project axons across the CNS-pe-ripheral nervous system (PNS) boundary, are attracted by meninges. Conver-sely, axons of both ipsi- and contralaterally projecting dorsal spinal cord inter-neurons are repelled by meninges. The responses of these axonal populations to the meninges are consistent with their trajectories relative to meninges in vivo, suggesting that meningeal guidance factors contribute to nervous system wiring and control which axons are able to traverse the CNS-PNS boundary.



90

P70

Title: Two receptor tyrosine phosphatases dictate the depth of the axon stabilizing layer in the Drosophila visual system

Presenting Author: Takashi SuzukiCo-Author(s): Satoko Hakeda-Suzuki, Hiroki Takechi, Hinata Kawamura

Abstract: Formation of a functional neuronal network requires not only precise target recognition, but also stabilization of axonal contacts within their appro-priate synaptic layers. However, little is known about the molecular mecha-nisms underlying the stabilization of axonal connections after reaching their specifically targeted layers. Here, we show that two receptor protein tyrosine phosphatases (RPTPs), LAR and Ptp69D, act redundantly in photoreceptor afferents to stabilize axonal connections to the specific layers of the Droso-phila visual system. Surprisingly, by combining loss-of-function and genetic rescue experiments, we found that the depth of the final layer of stable ter-mination relied primarily on the cumulative amount of LAR and Ptp69D cyto-plasmic activity, while specific features of their ectodomains contribute to the choice between two synaptic layers, M3 and M6, in the medulla. These data demonstrate how the combination of overlapping downstream but di-versified upstream properties of two RPTPs can shape layer specific wiring.



91

P71

Title: Microdeletions in MAST1 cause mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations

Presenting Author: Ratna TripathyCo-Author(s): Ines Leca, T. van Dijk, Bregje van Bon, Thomas Gstrein, Martin Breuss, Nadia Bahi-Buisson, Alex Paciorkowski, Alistair Pagnamenta, Jenny Taylor, Gaetano Terrone, Giuseppina Vitiello, Alessandra D’Amico, Ennio Del Giudice, Nicola Brunetti-Pierri, Alexandre Alexandre Reymond, Norine Voisin, Jonathan A. Bernstein, Ellyn Farrelly, Tyler Pierson, Usha Kini, Thomas Leo-nard, Linlea Armstrong, Susan Hiatt, Gregory Cooper, Ghayda Mirzaa, Tyler Pierson, Frank Baas, Jamel Chelly, Nick J. Cowan, David Anthony Keays

Abstract: Enlargement of corpus callosum is a strikingly neurological feature that has been associated with megalencephaly and mutations in the PI3K/AKT3/mTOR pathway. Here, we report that de novo mutations in MAST1 cau-se mega-corpus-callosum syndrome with cerebellar hypoplasia, and cortical malformations (MCC-CH-CM) in the absence of brain hypertrophy. Consistent with this phenotype an analysis of MAST1 expression reveals that it is found predominantly in post-mitotic neurons. Biochemical studies demonstrated that MAST1 is a microtubule associated protein and revealed that patient speci-fic mutations alter the affinity of the protein for microtubules. We further show that MAST1 knockout animals are phenotypically normal, whereas the deleti-on of a single amino acid (Leu278del) recapitulates the distinct neurological phenotype observed in patients. Our data indicate that MAST1 mutations act by a gain-of-function mechanism that is independent of the PI3K/AKT3/mTOR pathway. This work has uncovered the genetic lesion that causes MCC-CH-CM and highlights the importance of MAST proteins in neuronal development.



92

P72

Title: Genetic fate mapping of spinal commissural neurons

Presenting Author: Alastair TullochCo-Author(s): Shaun Teo, Julia Schoenewald, Marc Tessier-Lavigne, Alexan-der Jaworski

Abstract: Commissural neurons in the mouse embryonic spinal cord are a pri-me model system to study axon guidance. These neurons arise from multiple progenitor domains in the developing neural tube and settle in various laminae of the spinal cord. The unifying feature of these neurons is that they send axons across the ventral midline. After midline crossing, commissural axon trajectories diverge along the rostro-caudal axis, and rostrally-projecting axons ultimately innervate various supraspinal targets in the thalamus, mesencephalon, cere-bellum, and medulla. Thus, commissural neurons are a highly heterogeneous population of cells with respect to their cell body position, axonal trajectory, and neurotransmitter phenotype. Although the guidance of commissural axons during development has been studied in great detail, the mature phenotype of commissural neurons has not been characterized comprehensively. This is lar-gely due to extensive neuronal migration within the developing spinal cord and lack of a specific genetic marker to track commissural neurons.To follow the fate of commissural neurons from the embryonic into the adult mouse spinal cord, we generated mice expressing Cre recombinase from the Robo3 locus. Robo3 is an axon guidance receptor selectively expressed by all spinal commissural neurons, where it is required for axon crossing of the ventral midline. Here, we use Robo3Cre mice in combination with a Cre-dependent reporter line to elucidate the developmental origin of commissural neurons and characterize their positions and molecular makeup in the adult spinal cord. Our studies pro-vide insights into the development and ultimate fate of commissural neurons, and our Robo3Cre mice serve as an important genetic entry point for further analyses of commissural neuron development, connectivity, and function.



93

P73

Title: Prl-1 phosphatase controls spatial specificity of CNS synapse for-mation upstream of the InR/Akt/mTORC1 pathway

Presenting Author: Olivier UrwylerCo-Author(s): Azadeh Izadifar, Sofie Vandenbogaerde, Katlijn Vints, Anna Kremer, Dietmar Schmucker

Abstract: Precise subcellular and spatial control of synapse formation is es-sential for proper CNS development, yet this process is challenging to study in vivo due to the enormous complexity of the CNS. We use genetic tools and correlative light and electron microscopy (CLEM) to investigate synaptogenesis at single-neuron resolution in the Drosophila CNS. In an in vivo RNAi screen and subsequent validation with new loss-of-function mutations, we uncover-ed a role for Phosphatase of regenerating liver (Prl-1) in spatially restricted synapse formation in the CNS. Prl-1 promotes terminal arborization and sy-naptogenesis specifically in one out of three main axon branches of a defined mechanosensory neuron. CLEM and genetic data suggest that this occurs th-rough preventing excessive endocytosis. Molecularly, our results indicate that the synaptogenic function of Prl-1 involves positive regulation of the Insulin Receptor - Pi3K pathway, and downstream activity of Akt and the mTORC1 complex. Finally, we present evidence that the control of compartmentalized synaptogenesis occurs by Prl-1-mediated dephosphorylation of a membra-ne phospholipid, suggesting a mechanism for regulation of endocytosis and Akt activity. This work identifies novel functions for Prl-1, a phosphatase ex-tensively studied in the context of cancer metastasis, in CNS development.



94

P74

Title: Role of plexinB2 in cerebellar granule neuron development

Presenting Author: Eljo van BattumCo-Author(s): Céline Heitz, Alain Chédotal

Abstract: Cerebellar Granule Neurons (CGNs) are the most abundant neuro-nal population in the mouse brain. Their developmental sequence of prolife-ration, tangential and radial migration, and differentiation is stereotypical for many other types of neurons and mainly takes place during the first weeks after birth. Axon guidance proteins including several Plexins and Semaphorins are uniquely expressed in distinct cerebellar laminae, which might relate to their function. PlexinB2 (PlxnB2) is expressed exclusively in the outer external gra-nule layer (oEGL) in proliferating CGN precursors. PlxnB2-knockout mice show a severely disrupted lobular and laminar organization of the cerebellum, and ectopic proliferating CGNs in the molecular layer. In other cell types PlxnB2 is associated with proliferation and mitotic spindle organization, but is unknown how PlxnB2 regulates the transition between CGN proliferation and migrati-on, and how defected CGN localization leads to the severe lobular and lami-nation phenotype.To date, research into the role of PlxnB2 in postnatal cere-bellar development was difficult due to lethality of full PlxnB2 knockout mice. Recently, a novel conditional mouse model was developed which displays - when crossed with Engrailed1- or Wnt1Cre-lines - a clear PlxnB2-phenotype. Using 3DISCO we show that patches of CGNs remain at the cerebellar surface, and that the IGL has as a severely ruffled structure in the mutant. Interestingly, mutant EGL explants show a clear axon growth and fasciculation effect and aberrant neuron migration. We also discovered that mutant CGNs in vivo dis-play abnormal axon growth, -lamination and -fasciculation. In addition to in vivo electroporation, 3D-imaging and tissue culture techniques, we perform live-i-maging and biochemistry to study how PlxnB2 is involved in steering proper CGN proliferation, morphology and localization during cerebellar development.



95

P75

Title: circular RNA‘s: novel regulators of neuronal development

Presenting Author: Danielle van RossumCo-Author(s): R. Jeroen Pasterkamp

Abstract: Circular RNAs (circRNAs) are highly stable, circularized non-coding RNAs which are enriched in the nervous system and in specific subcellular compartments. Recent studies show that many circRNAs are expressed in a tissue/developmental-stage-specific manner and reveal a striking (up)regulati-on of circRNAs during neuronal and synaptic development. Interestingly, many circRNAs expressed in neural tissues derive from genes with prominent ro-les in early neural development, e.g. genes implicated in Wnt signaling and axon guidance. However, although a few circRNAs have been shown to bind microRNAs or RNA-binding proteins, the precise functions and mechanis-ms-of-action of most circRNAs are poorly understood. In our study, we inves-tigate circRNAs generated from genes implicated in axon guidance. We aim to characterize their expression patterns in the developing and adult nervous system and elucidate their neuronal function(s) using various in vitro and in vivo techniques. This is of interest as recent studies show that circRNA molecules substantially contribute to regulation of gene expression and that they may be involved in the development and progression of various neurological disorders.



96

P76

Title: Mouse genetics tools for studying Semaphorin6A reverse signaling

Presenting Author: Marieke G. VerhagenCo-Author(s): Suzanne Lemstra, Kati Rehberg, Youri Adolfs, R. Jeroen Paster-kamp

Abstract: The axon guidance molecule Semaphorin6A (Sema6A) plays a key role during the development of the nervous system. Sema6A is a transmem-brane protein that, depending on the molecular and cellular context, induces forward or reverse signaling. The precise mechanisms underlying Sema6A forward and reverse signaling incompletely understood. To study the receptor and ligand functions of Sema6A, we generated a new transgenic mouse mo-del (Sema6A?cyto) lacking the Sema6A intracellular domain, which is essen-tial for its receptor function, using the Cre/Lox system. In this mouse model, Sema6A only acts as a ligand. To establish when and where Sema6A acts as a receptor, we performed immunohistochemistry on Sema6A?cyto mutant mice for a variety of cellular and axonal markers. This analysis reveals de-velopmental defects in a variety of brain regions. To further study the signa-ling molecules that act downstream Sema6A we performed immunoprecipita-tion followed by mass spectrometry and biochemical analyses. These findings indicate that Sema6A receptor functions are essential for proper develop-ment of several brain regions and axonal tracts and begin to provide insight into the signaling pathways downstream of the transmembrane semaphorin.



97

P77

Title: Dysregulation of circular RNAs and axonal defects in spinal mu-scular atrophy

Presenting Author: Mark VerheijenCo-Author(s): S. Zijlstra, R. Vieira de Sá, S. Kling, W.L. van der Pol, R.J. Pas-terkamp

Abstract: Spinal muscular atrophy (SMA) is a degenerative neuromuscular dis-order and a leading genetic cause of infant death. The disease is characterized by loss of ?-motor neurons in the anterior horn of the spinal cord, resulting in progressive muscle atrophy and weakness. SMA is most frequently caused by homozygous loss of the SMN1 gene, which encodes for the widely expressed survival motor neuron (SMN) protein. Previous studies have suggested SMN to be a versatile ribonucleoprotein (RNP) assembly hub and have demonst-rated the involvement of SMN in various cellular processes, mainly related to RNA metabolism. These include pre-mRNA splicing, through its role in small nuclear RNP formation, neuronal transport and localization of RNAs and con-trol of local protein synthesis. However, it remains unknown how loss of SMN exactly causes motor neuron disease. In order to gain new insights into the axonal functions of SMN, we analyzed SMN protein binding partners. As ex-pected, we found SMN to be bound to many RNA-binding proteins present in axonal projections. Interestingly, we identified SMN as a putative constituent of circular RNA (circRNA)-protein complexes (circRNPs). circRNAs constitute a class of single-stranded RNA that has recently attracted wide interest due to their emerging roles in regulation of eukaryotic gene expression. They are generated through “back-splicing” events, wherein 5’ and 3’ ends are spliced together to form a covalently closed loop structure. Their remarkable structure provides them with properties that distinguish them from linear RNA isoforms, e.g., increased stability and gene regulatory potency. circRNAs are particular-ly abundant in the nervous system, being actively transported into axons and growth cones, hinting at neuron-specific functions. By measuring circRNA ex-pression levels in SMN-deficient human induced pluripotent stem cell (hiP-SC)-derived motor neurons from patients and in healthy controls, we found that circRNA expression is altered in SMA. We surmise that SMN levels af-fect circRNA biogenesis and functionality and that dysregulation of circRNAs might contribute to axonal dysfunction in SMA. We are currently further ex-ploring a link between SMN levels, pre-mRNA splicing defects, circRNAs and axon-specific functional impairment in different experimental models for SMA.



98

P78

Title: Identifying the role of DCC in the postnatal development of the visual system

Presenting Author: Robin VigourouxCo-Author(s): Kim Nguyen-Ba-Charvet, Alain Chedotal

Abstract: A major goal in neuroscience is to understand how sensory informa-tion is processed. The mammalian visual system is an ideal model to address this question. The retina is a highly organized structure divided into 3 distin-ct nuclear layers and 2 synaptic areas. Light is converted by photoreceptors into an electrical signal collected by bipolar cells and then relayed to Retinal Ganglion Cells (RGC) which exit the retina and innervate different brain tar-gets. RGCs from the retina project to multiple visual brain nuclei via a single tract, the optic nerve. The transmembrane receptor Deleted in Colorectal Can-cer (DCC) is expressed by RGCs and has been shown to be critical for the formation of the optic nerve by responding to its ligand, Netrin-1, expressed at the optic disc. Indeed, both Netrin-1 hypomorphs and DCC knockout mice show optic nerve hypoplasia. Due to the lethality of both mutants, the study of these molecules has been restricted to embryonic stages. However, at birth, the visual system is far from being fully developped. Indeed, half of the retinal cell types still have to differentiate. Moreover, axonal arborization and refine-ment in brain nuclei all occur in the first postnatal week. Our data shows that contrary to what was previously described, DCC expression within the retina is much broader. Indeed, DCC expression is initially restricted to differentia-ting RGCs but is then highly expressed in both nuclear layers as well as both synaptic layers of the retina in early postnatal stages. To understand the role of DCC within the retina, we created a conditional deletion of DCC under the Dickopf-3 (Dkk3) promoter which is expressed in retinal progenitors cells, Dk-k3:Cre;DCClox/lox. These mutants are viable and adult mice show a dramatic thinning of the retina characterized by the absence of an RGC layer as well as photoreceptor degeneration. We are currently adopting both genetic and viral approaches to remove DCC in particular retinal neurons to study the precise mechanism responsible for the degeneration of both RGCs and Photoreceptors.



99

P79

Title: Mechanisms of co-adaptation ensuring targeting precision in topo-graphic guidance

Presenting Author: Franco WethCo-Author(s): Felix Fiederling, Markus Weschenfelder, Lisa Kornstaedt, Martin Bastmeyer

Abstract: Topographic axonal maps, which preserve neighborhood relations-hips upon projection constitute a major wiring pattern of the brain. Topographic growth cone (GC) targeting uses quantitative address codes derived from gra-ded distributions of guidance cues. Thus, in the paradigmatic retinotectal sys-tem, ephrin-As and EphAs are counter-graded along the anterior/posterior axis of both, the retina and the tectum. Due to the bidirectional signaling capability of the ephrin/Eph system, this expression pattern gives rise to six dimensions of signaling (fiber/target forward (fwd) and reverse (rev), FF fwd and rev, cis fwd and cis rev). We have previously shown theoretically and experimentally, that a model based on the GCs seeking a balance of total rev vs. total fwd signaling can explain a substantial body of evidence gained on this systems over decades of research. Recently, we found, that despite the requirement of quantitative signaling precision, retinal GCs robustly adapt towards the topo-graphic cues. By extending our model to include adaptation and by tailored in-vitro assays, we showed that this conflict is solved through a peculiar novel mechanism of adaptation (“co-adaptation”), in which the participating signa-ling channels adapt concomitantly and in strict proportion irrespective of their individual activation states. Our experiments suggest a working hypothesis on the mechanisms of co-adaptation. Ephrin-As and EphAs are supposed to resi-de in separate microdomains of the GC membrane. Upon adaptive signaling, they are released proportionately into the non-raft domain, from where they are endocytosed in a clathrin-dependent manner. According to our modeling, this generates cis-signaling endosomes drowning external trans-signals as a primary desensitization response. Using orthogonal self-labeling peptides as localization probes for ephrin-As and EphAs and pharmacological inhibitors, we are currently trying to verify the individual steps of the suggested mechanism.



100

P80

Title: Gbx2 regulates the development of a novel amacrine cell subtype in the mammalian retina

Presenting Author: Kevin WrightCo-Author(s): Patrick C. Kerstein, Joseph Leffler, W. Rowland Taylor

Abstract: Understanding how neurons connect to one another during develop-ment to form functional circuits remains a major challenge. With more than 60 distinct cell types, highly stereotyped synaptic lamina and well-defined physio-logy, the retina provides an ideal model for studying neural circuit development. Based on morphological and physiological criteria, there are at least 30 distinct types of inhibitory amacrine cells (ACs) within the retina. However, a lack of ge-netic tools to label and manipulate these distinct subpopulations has hampered our understanding of how they develop and wire into functional circuits.Using genetic approaches, we have found that expression of the transcription factor Gbx2 identifies a specific population of ACs. Gbx2+ AC cells are located in both the inner nuclear layer (INL) and ganglion cell layer (GCL), and have asymme-tric medium to wide field dendritic arbors that stratify selectively in sublamina 3 and 5 within the inner plexiform layer (IPL). Gbx2+ ACs do not express either of the main inhibitory neurotransmitters, marking them as a unique subpopulation of non-GABAergic, non-Glutamatergic (nGnG) ACs. Gbx2+ ACs are coupled to neighboring cells via gap junctions, suggesting that their synaptic output may be through electrical synapses. Using a combination of electrophysiology and pharmacology, we determined that Gbx2+ ACs receive direct input from GA-BAergic and Glutamatergic neurons and exhibit transient responses to both ON and OFF light stimuli. Conditional deletion of Gbx2 indicates that it is required for the proper dendritic stratification of Gbx2+ ACs. Ongoing experiments are investigating how deletion of Gbx2 affects the morphological and physiological properties of these neurons, as well as identifying the downstream targets of Gbx2. Together, these results genetically identify a novel AC subtype, and pro-vide a model for studying transcriptional control of neural circuit development.



101

3. General information



102

3.1 Conference Dinner

The conference dinner will take place at Redlinger Hüttewww.redlingerhuette.at

Meeting Point: September 13, 18:10, Terrace in front of Raiffeisen Lecture Hall

A very nice, 20-minute walk through the woods from IST Austria toRedlinger Hütte, 3400 Kierling (see map below)



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3.2 Guided Tour

The Organizing Committee is offering a guided tour for all conference partici-pants for free.

Date: September 14 (08:00 - 16:00)

Destination: Dürnstein in the Wachau region, which belongs to Austria's UNESCO World Cultural Heritage sites

Program08:00 Shuttle bus pick up from Wien Heiligenstadt 08:30 Stop at Niedermarkt Klosterneuburg & IST Austria08:30 Shuttle bus pick up Hotel Marienhof08:45 Drive to Dürnstein10:00-12:00 Guided tour through Dürnstein’s castle ruins and monastery12:00-14:00 Lunch at the “Heurigen”, a typical Austrian restaurant 14:00 Bus trip back15:00 Drop off IST Austria - Niedermarkt Klosterneuburg 15:45 Drop Off Wien Heiligenstadt

Located along the famous Danube in Lower Austria, Dürnstein is well-known for its wineries and is one of the most popular tourist destinations in the Wachau region. The city’s name literally means “dry castle” in German, presumably after the stone castle situated high above the main town area.

The town was first mentioned in 1019 and gained notoriety in late 1192 when Richard the Lionheart was held captive in the castle by Duke Lepold V of Austria. It was officially made a town in 1476, and is well-known for the 1805 Battle of Dürnstein that took place just outside the city.



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4. Orientation & Transport



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4.1 Map of Klosterneuburg

A Niedermarkt Klosterneuburg (Bus Station)B Hotel SchrannenhofC Hotel Restaurant AnkerD Bürgerhaus SalmeyerE Frühstückspension Alte Mühle F Hotel Höhenstraße G Hotel MarienhofH IST Austria



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4.2 Conference Location: Raiffeisen Lecture Hall (RLH, Building 02)

Institute of Science and Technology Austria (IST Austria)Am Campus 1, 3400 Klosterneuburg, Phone: +43 2243 9000



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4.3 Around IST Austria

The area around IST Austria offers a variety of recreational activities. You can walk along the Danube, or hike through the forests of the Buchberg and reward yourself with an unforgettable panoramic view of Klosterneuburg.

• BILLA supermarket, open Mon-Fri 7:15-19:30, Sat 7:15-18:00.

• Museum Gugging www.gugging.org 5-minute walk from IST Austria

• Stift Klosterneuburg (monastery) www.stift-klosterneuburg.at 10-minute walk from Niedermarkt Klosterneuburg

• Happyland - Klosterneuburg’s sports centre www.happyland.cc 5-minute walk from Niedermarkt Klosterneuburg

• Redlinger Hütte, www.redlingerhuette.at, a very nice, 20-minute walk through the woods from IST, daily menu

• Der Waldhof (Austrian cuisine), www.der-waldhof.at 10 am - 10 pm, closed on Mondays, 20-minute walk from IST



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4.4 Hotels Hotel Schrannenhof****3400 Klosterneuburg, Niedermarkt 17-19+43 2243 [email protected] , www.schrannenhof.at

Hotel Restaurant Anker***3400 Klosterneuburg, Niedermarkt 5+43 2243 [email protected], www.hotel-anker.at Bürgerhaus Salmeyer3400 Klosterneuburg, Stadtplatz 17+43 2243 32146 [email protected], www.buergerhaus-salmeyer.at

Frühstückspension Alte Mühle***3400 Klosterneuburg, Mühlengasse 36+43 2243 [email protected], www.hotel-altemuehle.at Hotel Höhenstraße***3400 Klosterneuburg, Kollersteig 6+43 2243 [email protected], www.hotel-hoehenstrasse.at

Hotel Marienhof***3413 Unterkirchbach 32+43 2242/[email protected], www.marienhof-wien.com



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4.5 Conference Shuttles Conference Shuttles

The Organizing Committee provides 3 conference shuttles to go to and from IST Austria.

Conference Shuttle 1 (Wien Heiligenstadt – Hotel Höhenstraße - IST Austria): All participants who have booked their accommodation in Vienna or stay at Hotel Höhenstraße should use conference shuttle 1. The regular IST shuttle bus (# 142) is very crowded in the morning.

Conference Shuttle 2 (Niedermarkt Klosterneuburg – Pension Alte Mühle - IST Austria): All participants who have booked their accommodation in downtown Kloster-neuburg or stay at Pension Alte Mühle should use conference shuttle 2.

Conference Shuttle 3 (Hotel Marienhof – IST Austria): All participants who have booked their accommodation at Marienhof should use conference shuttle 3, which is provided by Hotel Marienhof.



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4.6 Public Transportation to IST Austria

IST Shuttle (Bus #142) IST Austria provides a shuttle bus for anybody traveling from Wien Heiligenstadt to the campus (and return) to expand the public bus service. The IST Austria Shuttle Bus connects the underground network (U4 Heiligenstadt) and IST Austria with only one stop at Kloster-neuburg Stadtplatz. That leads to a reduction in traveling time compa-red to the public bus. The IST Shuttle takes 22 minutes from Heiligenstadt and runs Monday-Friday. It is, however, very crowded in the mornings and evenings, so please use the provided conference shuttle busses. The public busses take 30 minutes from Heiligenstadt to IST Austria.

IST Shuttle #142If you decide to take the IST Shuttle Bus, please present the Shuttle Bus invitation below (page 112). Printed invitations can be picked up at the Registration desk.

Public Bus #239 (please note: please check direction, it needs to go to MARIA GUGGING if going to IST Austria!) Tickets can be purchased on the bus.



111

Bus Schedule IST Shuttle #142, Public Bus to IST Austria

MONDAY - FRIDAY (except Austrian bank holiday)

First 239 239 439 239 239 239

IST 142 239

IST 142

239 & 341 C

IST 142 239

IST 142 239

IST142 239

IST 142 239

IST142 239 239

IST142 239 239

IST142 239 239

IST142 239 239

IST142 239

Departure from Heiligenstadt/Vienna 06.00 06.10 06.30 06.40 07.00 07.10 07.17 07.30 07.47 08.00 08.17 08.30 08.47 09.00 09.17 09.30 09.47 10.00 10.17 10.30 11.00 11.17 11.30 12.00 12.17 12.30 13.00 13.17 13.30 14.00 14.17 14.30

Departure from Stadtplatz Klosterneuburg 06.18 06.33 06.51 07.03 07.18 07.33 07.31 07.48 08.01 08.18 08.31 08.48 09.01 09.18 09.31 09.48 10.01 10.18 10.31 10.48 11.18 11.31 11.48 12.18 12.31 12.48 13.18 13.31 13.48 14.18 14.31 14.48

Arrival at Maria Gugging/IST Austria 06.30 06.45 07.03 07.15 07.30 07.45 07.39 08.00 08.09 08.30 08.39 09.00 09.09 09.30 09.39 10.00 10.09 10.30 10.39 11.00 11.30 11.39 12.00 12.30 12.39 13.00 13.30 13.39 14.00 14.30 14.39 15.00

239IST142 239 239 239 239

IST142 239 239 239 239

IST142 239 239

ST142 239 239

IST142 239

IST142 239

IST142 239 239

IST142 239 239 239 239 239 239 239 239

Last 239

Departure from Heiligenstadt/Vienna 15.00 15.17 15.30 15.40 16.00 16.10 16.17 16.30 16.40 17.00 17.10 17.17 17.30 17.40 17.47 18.00 18.10 18.17 18.30 18.47 19.00 19.17 19.30 20.00 20.17 20.30 21.00 21.30 22.00 22.30 23.00 23.30 00.00 00.47

Departure from Stadtplatz Klosterneuburg 15.18 15.31 15.48 16.03 16.18 16.33 16.31 16.48 17.03 17.18 17.33 17.31 17.48 18.03 18.01 18.18 18.33 18.31 18.48 19.01 19.18 19.31 19.46 20.13 20.31 20.43 21.13 21.43 22.13 22.43 23.13 23.43 00.13 01.00

Arrival at Maria Gugging/IST Austria 15.30 15.39 16.00 16.15 16.30 16.45 16.39 17.00 17.15 17.30 17.45 17.39 18.00 18.15 18.09 18.30 18.45 18.39 19.00 19.09 19.30 19.39 19.55 20.22 20.39 20.52 21.22 21.52 22.22 22.52 23.22 23.52 00.22 01.09

First 239 239 239 239 239 239 239 239 239 239 239 C 239 C 239

IST142 239

IST142 239

IST142 239

IST 142 239

IST142 239 239

IST142 239 239

IST142 239 239

IST142 239 239

Departure from Maria Gugging/IST Austria 04.58 05.11 05.26 05.41 05.56 06.11 06.27 06.42 06.57 07.12 07.24 07.27 07.42 07.43 08.12 08.18 08.42 08.54 09.12 09.24 09.42 09.54 10.12 10.42 10.54 11.12 11.42 11.54 12.12 12.42 12.54 13.12 13.42

Departure from Stadtplatz Klosterneuburg 05.08 05.21 05.36 05.51 06.06 06.21 06.39 06.54 07.09 07.24 07.36 07.39 07.54 07.51 08.24 08.26 08.54 09.02 09.24 09.32 09.54 10.02 10.24 10.54 11.02 11.24 11.54 12.02 12.24 12.54 13.02 13.24 13.54

Arrival Heiligenstadt/Vienna 05.25 05.40 05.55 06.15 06.23 06.45 07.00 07.15 07.30 07.45 07.53 08.00 08.15 08.16 08.45 08.46 09.15 09.16 09.45 09.46 10.15 10.16 10.45 11.15 11.16 11.45 12.15 12.16 12.45 13.15 13.16 13.45 14.15

IST142 239 239

IST142 239 239

IST142 239 239 239

IST142 239 239

IST 142 239

IST142 239 239

IST

142 239IST142

239 & 439

IST142 239

IST

142 239 239IST 142 239 239 239 239 239 239

Last 239

Departure from Maria Gugging/IST Austria 13.54 14.12 14.42 14.54 15.12 15.42 15.54 16.12 16.25 16.42 16.54 16.55 17.12 17.24 17.42 17.54 17.57 18.12 18.24 18.42 18.54 18.57 19.24 19.33 19.54 20.03 20.33 20.54 21.03 21.33 22.03 22.33 23.03 23.33 00.03

Departure from Stadtplatz Klosterneuburg 14.02 14.24 14.54 15.02 15.24 15.54 16.02 16.24 16.37 16.54 17.02 17.07 17.24 17.32 17.54 18.02 18.09 18.24 18.32 18.54 19.02 19.09 19.32 19.44 20.02 20.14 20.44 21.02 21.14 21.44 22.14 22.44 23.14 23.44 00.14

Arrival Heiligenstadt/Vienna 14.16 14.45 15.15 15.16 15.45 16.15 16.16 16.45 16.55 17.15 17.16 17.25 17.45 17.46 18.15 18.16 18.25 18.45 18.46 19.13 19.16 19.28 19.46 19.58 20.16 20.28 20.58 21.16 21.28 21.58 22.28 22.58 23.28 23.58 00.28

SATURDAY (except Austrian bank holidays)

First 239 239 239 239 239 239 239 239 239 239 239 239 239 239 239 239 239 239 239 239 239 239 239 239 239 239 239 239 239 239 239 239 239 239 239 239 239

Last 239

Departure from Heiligenstadt/Vienna 06.00 06.30 07.00 07.30 08.00 08.30 09.00 09.30 10.00 10.30 11.00 11.30 12.00 12.30 13.00 13.30 14.00 14.30 15.00 15.30 16.00 16.30 17.00 17.30 18.00 18.30 19.00 19.30 20.00 20.30 21.00 21.30 22.00 22.30 23.00 23.30 00.00 00.47

Departure from Stadtplatz Klosterneuburg 06.18 06.51 07.18 07.48 08.18 08.48 09.18 09.48 10.18 10.48 11.18 11.48 12.18 12.48 13.18 13.48 14.18 14.48 15.18 15.48 16.18 16.48 17.18 17.48 18.18 18.48 19.18 19.48 20.13 20.43 21.13 21.43 22.13 22.43 23.13 23.43 00.13 01.00

Arrival at Maria Gugging/IST Austria 06.30 07.03 07.30 08.00 08.30 09.00 09.30 10.00 10.30 11.00 11.30 12.00 12.30 13.00 13.30 14.00 14.30 15.00 15.30 16.00 16.30 17.00 17.30 18.00 18.30 19.00 19.30 20.00 20.22 20.52 21.22 21.52 22.22 22.52 23.22 23.52 00.22 01.09

First 239 239 239 239 239 439 239 239 439 239 239 239 239 239

239 & 439 239 239

239 & 439 239 239 239 239 239 239 341 239 239 239 239 239 239 239 239 239 239 239 239 239 239

Last 239

Departure from Maria Gugging/IST Austria 05.12 05.42 06.12 06.42 07.12 07.26 07.42 08.12 08.42 09.12 09.42 10.12 10.42 11.12 11.42 12.12 12.42 13.12 13.42 14.12 14.42 15.12 15.42 16.12 16.42 17.12 17.42 18.12 18.42 18.57 19.33 20.03 20.33 21.03 21.33 22.03 22.33 23.03 23.33 00.03

Departure from Stadtplatz Klosterneuburg 05.24 05.54 06.24 06.54 07.24 07.38 07.54 08.24 08.54 09.24 09.54 10.24 10.54 11.24 11.54 12.24 12.54 13.24 13.54 14.24 14.54 15.24 15.54 16.24 16.54 17.24 17.54 18.24 18.54 19.09 19.44 20.14 20.44 21.14 21.44 22.14 22.44 23.14 23.44 00.14

Arrival Heiligenstadt/Vienna 05.45 06.15 06.45 07.15 07.45 08.00 08.15 08.45 09.15 09.45 10.15 10.45 11.15 11.45 12.15 12.45 13.15 13.45 14.15 14.45 15.15 15.45 16.15 16.45 17.15 17.45 18.15 18.45 19.13 19.28 19.58 20.28 20.58 21.28 21.58 22.28 22.58 23.28 23.58 00.28

SUNDAY & AUSTRIAN BANK HOLIDAYS

First 239 239 239 239 239 239 239 239 239 239 239 239 239 239 239 239 239 239 239 239 239 239 239 239 D

Last 239 D

Departure from Heiligenstadt/Vienna 06.30 07.30 08.30 09.30 10.30 11.30 12.30 13.00 13.30 14.30 15.00 15.30 16.30 17.00 17.30 18.00 18.30 19.00 19.30 20.00 21.00 22.00 23.00 00.00 00.47

Departure from Stadtplatz Klosterneuburg 06.48 07.48 08.48 09.48 10.48 11.48 12.48 13.18 13.48 14.48 15.18 15.48 16.48 17.18 17.48 18.18 18.48 19.18 19.48 20.13 21.13 22.13 23.13 00.13 01.00

Arrival at Maria Gugging/IST Austria 07.00 08.00 09.00 10.00 11.00 12.00 13.00 13.30 14.00 15.00 15.30 16.00 17.00 17.30 18.00 18.30 19.00 19.30 19.57 20.22 21.22 22.22 23.22 00.22D 01.09D

First 239 239 239 239 239 239 239 239 239 239 239 A 239 239 A 239 239 239 239 239 A/B 239 239 239 239 239 239

Last 239

Departure from Maria Gugging/IST Austria 06.12 07.12 08.12 09.12 10.12 11.12 12.12 13.12 13.42 14.12 14.42 15.12 15.42 16.12 16.42 17.12 17.42 18.02 18.27 18.57 20.03 21.03 22.03 23.03 00.03

Departure from Stadtplatz Klosterneuburg 06.24 07.24 08.24 09.24 10.24 11.24 12.24 13.24 13.54 14.24 14.54 15.24 15.54 16.24 16.54 17.24 17.54 18.14 18.39 19.09 20.14 21.14 22.14 23.14 00.14

Arrival Heiligenstadt/Vienna 06.45 07.45 08.45 09.45 10.45 11.45 12.45 13.45 14.15 14.45 15.45 16.45 17.15 17.45 18.15 18.35B 18.58 19.28 20.28 21.28 22.28 23.28 00.28

142: Heiligenstadt/Vienna - Maria Gugging/IST Austria 239: Heiligenstadt/Vienna - Maria Gugging 341/439: Heiligenstadt/Vienna - Maria Gugging - Tulln

Please note that not all buses of the line 239 go to Maria Gugging/IST Austria! Please check the display above the windshield for the fi nal stop.

The fi nal stop displayed must be “Maria Gugging” in order to reach the IST Austria Campus!You will not reach the IST Austria Campus if the fi nal stops Rathausplatz or Klosterneuburg-Kierling are displayed!

Point of departure/arrival

Bus line


Bus line


Bus line


Bus line


Bus line


Bus line


Bus line


Bus line

IST AUSTRIA SHUTTLE BUS PRICES (valid as of July 06, 2016)

IST Austria shuttle bus prices for regular passengers.

One-way ticket ADULT

16 years and older

One-way ticket CHILDREN

6years - compledet age of 15 years

Vienna/Heiligenstadt - Klosterneuburg/Stadtplatz - IST AUSTRIA/Maria Gugging ORIST AUSTRIA/Maria Gugging - Klosterneuburg/Stadtplatz - Vienna/Heiligenstadt

(Price valid in case you DID NOT purchase a ticket for Vienna)

€ 4,10 € 2,20

Vienna/Heiligenstadt - Klosterneuburg/Stadtplatz - IST AUSTRIA/Maria Gugging ORIST AUSTRIA/Maria Gugging - Klosterneuburg/Stadtplatz - Vienna/Heiligenstadt

(Price valid in case you already purchased a ticket for Vienna)

€ 1,90 € 1,10

Children (0 – completed age of 6 years) FREE

Children with a “Jugendticket / TOP-Jugendticket” have to pay a surcharge of € 0,20 to use the IST Austria shuttle bus.

IST Austria assumes no liability for the content above. All content is subject to change.

Offi cial bus schedule can be found on www.vor.at

IST AUSTRIA SHUTTLE BUS / 10.04.2017

A = Only goes to trainstation Kierling (1min more than Stadtplatz Klosterneuburg, please use afterwards the train B = March 26 until October 28, 2017, otherwise only goes to trainstation Kierling ; C = Only on days when there is NO school D = Stop only to exit



112

Symposium/Conference

Molecular and Cellular Mechanisms of NeuralCircuit Assembly Conference (AXON2017)

Host: Simon Hippenmeyer

Short Description: The European Conference on Molecular and Cellular Mechanisms of NeuralCircuit Assembly (AXON2017) will take place on the campus of the Institute of Science andTechnology Austria (IST Austria) in Klosterneuburg near Vienna on September 11-14, 2017 with200 anticipated conference attendees. For more info, please visit: http://ist.ac.at/axon2017

Mon, September 11, 2017 08:00am - Wed, September 13, 2017 09:00pmIST Austria Campus Raiffeisen Lecture Hall, Central Building

This invitation is valid as a ticket for the IST Shuttle from and to Heiligenstadt Station. Please find a schedule of the IST Shuttle on our

webpage (note that the IST Shuttle times are highlighted in dark green):

http://ist.ac.at/fileadmin/user_upload/pdfs/IST_shuttle_bus.pdf The IST Shuttle bus is marked IST Shuttle (#142) and has the Institute

Logo printed on the side.

www.ist.ac.at | Institute of Science and Technology Austria | Am Campus 1 | 3400 Klosterneuburg



113

4.7 Transportation in Vienna

Vienna has efficient public transport consisting of subways (U-Bahn), trams (Stra-ßenbahn) and busses. A single ticket is valid on all means of transport except for the airport (CAT) train. Tickets are bought at the ticket machines located in every subway station and need to be validated by stamping them at the small blue boxes at the entry to the subway platform or inside the trams and busses respectively (subway map is attached). Check www.wienerlinien.at for further information.

For going to the airport, you can either take a cab from IST Austria (approx. 45 minutes-1 hour), or go by public transport (shuttle bus or public bus) to U4 Heiligenstadt, take the U4 line to the stop Landstraße-Wien Mitte, and the direct CAT airport train to the airport (altogether approx. 1 ½ hours)

4.8 TaxisFor a cab from IST Austria to Heiligenstadt (U4 stop), Vienna downtown or the airport (best to have cash ready, an ATM is located in the lobby of the Central Building on IST Austria’s campus):

• Taxi Danzinger (www.taxi-danzinger.at, +43 2243 202 20, +43 676 666 50 70, about 55 EUR to the airport)• Taxi Glück (www.konlechner.at/glueck, +43 2243 361 11, +43 664 224 88 20, about 55 EUR to the airport)• ask at the IST Austria reception for help

You can take a cab from the airport directly to IST Austria, but be sure to have the full address of the Institute at hand: IST AustriaAm Campus 13400 Maria Gugging-Klosterneuburg



114



115

5. Contact & Organizing Committee



116

5.1 Local Organizing Committee Academic: Simon Hippenmeyer [email protected] Phone: +43 2243 9000 5101 Mobile: +43 664 883 49 216

Local Arrangements/Organizational: Marion Holl [email protected] Phone: +43 2243 9000 1132 Mobile: +43 650 533 10 24

Registration & Payment: Arinya Eller [email protected] Phone: +43 2243 9000 1121 Mobile: +43 699 811 56 355



117

5.2 List of Participants Name Email Address AffiliationAckerman Sarah [email protected] University of

OregonAdnan Gee [email protected] King‘s College

LondonAkkermans Onno [email protected] University of

OxfordAksu Metin [email protected] University of

OxfordAmberg Nicole [email protected] IST AustriaSøren S. L. Andersen [email protected] SciLifeLab, Upp-

sala UniversityArgentini Manuela [email protected] Institut de la Vision

- FVEArlotta Paola [email protected] Harvard UniversityAuer Albert [email protected] IST AustriaBadurek Sylvia [email protected] Vienna Biocenter

Core Facilities GmbH

Bagley Joshua [email protected] IMBABagni Claudia [email protected] University of

LausanneBashaw Greg [email protected] University of

PennsylvaniaBastmeyer Martin [email protected] Karlsruhe Institute

of TechnologyBeattie Robert [email protected] IST AustriaBergkirchner Beate [email protected] University of

ViennaBhowmick Tuhin [email protected] European Mo-

lecular Biology Laboratory

Bin Jenea [email protected] University of Edin-burgh

Bocanegra Laura [email protected] IST Austria



118

Name Email Address AffiliationBonanomi Dario [email protected] San Raffaele

Scientific InstituteBornstein Bavat [email protected] Weizmann

Institute of ScienceBorrell Victor [email protected] Universidad

Miguel HernandezBrand Andrea [email protected] University of

CambridgeBrunet Isabelle [email protected] INSERM U1050 -

College De FranceCampbell Michael [email protected] Luis [email protected] University of

SussexCharest Julien [email protected] IMPCharron Fred [email protected] IRCM/McGill

UniversityChedotal Alain [email protected] Institut de la VisionClarke Jon [email protected] King‘s College

LondonCochella Luisa [email protected] IMPColombo Gloria [email protected] IST AustriaContreras Ximena [email protected] IST AustriaCossart Rosa [email protected] INMEDCroteau Louis-Phi-lippe

[email protected] Institut de Recher-ches Cliniques de Montreal

Darwin Arulseeli Divya

[email protected] UMC Utrecht

De Marco Garcia Natalia

[email protected] Weill Cornell Medical College

Del Toro Daniel [email protected] Max Planck Institu-te of Neurobiology



119

Name Email Address AffiliationDelogu Alessio [email protected] King‘s College

London

Di Bonito Maria [email protected] Institute of Biology Valrose/Univer-site Nice Sophia Antipolis

Dlugosz Paula [email protected] Medical Univerity of Vienna

Drescher Uwe [email protected] King‘s College London

Duellberg Christian [email protected] IST AustriaDumoulin Alexandre [email protected] Max-Delbrueck-

Center Berlin

Dumstrei Karin [email protected] The EMBO Journal

Dun Xin-peng [email protected] Plymouth Uni-versity Peninsula Schools of Medici-ne and Dentistry

Erskine Lynda [email protected] University of Aberdeen

Escalante Augusto [email protected] Max Planck Institu-te of Neurobiology

Fishell Gordon [email protected] Harvard UniversityGiniger Edward [email protected] NIH (USA)Gomes da Silva Carla [email protected] University of Liege

Gonzalez-Calvo Ines [email protected]

CIRB-College de France

Gudjonsdottir Ragn-heidur

[email protected] University of Sussex

Guillemot Francois [email protected] The Francis Crick Institute

Guthrie Sarah [email protected] University of Sussex

Hahn Christian [email protected] Dept. Bioelectro-nics, Vienna



120

Name Email Address AffiliationHaimson Baruch [email protected] The Hebrew Uni-

versity Hadassah Medical School

Hansen Andi [email protected] IST AustriaHassan Bassem [email protected] VIBHe Yue [email protected] Karlsruhe Institute

of TechnologyHerrera Gonzalez De Molina Eloisa

[email protected] Instituto de Neu-rociencias CSIC-UMH

Hippenmeyer Simon [email protected] IST AustriaHolguera Lopez Isabel

[email protected] New York University

Huang Zengjin [email protected] VIB-KU Leuven Center for Brain & Disease Research

Hummel Thomas [email protected] University of Vienna

Jabinet Laura [email protected] University of Zurich

Javorski Dominik [email protected] University of Vienna

Jaworski Alexander [email protected] Brown UniversityJones E. Yvonne [email protected] University of

OxfordJösch Maximilian [email protected] IST AustriaKaltschmidt Julia [email protected] MSKCCKania Artur [email protected] IRCM / McGill /

U de MontrealKaur Rashmit [email protected] University of

ViennaKeays David [email protected] Research Institu-

te for Molecular Pathology



121

Name Email Address AffiliationKicheva Anna [email protected] IST AustriaKlar Avihu [email protected] The Hebrew Uni-


Klein Ruediger [email protected] Max-Planck Insti-tute of Neurobio-logy

Koelsch Yvonne [email protected] Max Planck Institu-te of Neurobiology

Kozak Sandra [email protected] EMBL HamburgLaukoter Susanne [email protected] IST AustriaLemstra Suzanne [email protected] UMC UtrechtLevesque Martin [email protected] Universite LavalLindenhofer Dominik [email protected] IMBALopez Bendito Guil-lermina

[email protected] Agencia Estatal Consejo Superior de Investigaciones Científicas

Louail Alice [email protected] UPMC - Institut de la Vision

Luo Liqun [email protected] Stanford UniversityLyons David [email protected] University of

EdinburghMarc Freeman [email protected] Vollum InstituteMastick Grant [email protected] University of

NevadaMayer Simone [email protected] University of

CaliforniaMayseless Oded [email protected] Weizmann Institu-

te of Science McCabe Brian [email protected] EPFL

Meijers Rob [email protected] EMBL Hamburg



122

Name Email Address AffiliationMeir Oren [email protected] The Hebrew Uni-


Minkina Olga [email protected] New York University

Monje Michelle [email protected] Stanford University

Monk Kelly [email protected] Washington Uni-versity

Mora García Natalia [email protected] Institut du Cerveau et de la Moelle Epinière

Morelli Giovanni [email protected] University of LiegeMorenilla Palao Cruz [email protected] Instituto de Neuro-

ciencias-UMH-C-SIC

Nguyen-Ba-Charvet Kim

[email protected] UPMC - Institut de la Vision

Ngyuen Laurent [email protected] University of LiegeNicol Xavier [email protected] Institut de la Vision

- FVENimpf Johannes [email protected] MFPLOzkan Engin [email protected] University of

Chicago

Pauler Florian [email protected] IST Austria

Phillips Alexander [email protected] IMP

Pignata Aurora Valeria

[email protected] INMG - Université Claude Bernard Lyon

Pinto-Teixeira Filipe [email protected] New York University

Pokusaeva Victoria [email protected] IST AustriaQuan Xiaojiang [email protected] ICMRamaekers Ariane [email protected] ICM



123

Name Email Address AffiliationRathjen Fritz G. [email protected] Max-Delbrueck-

CenterRebsam Alexandra [email protected] INSERM U839 -

IFMRomanov Roman [email protected] Medical University

of ViennaRos Oriol [email protected] UPMC - Institut de

la VisionSalecker Iris [email protected] The Francis Crick

InstituteSalesse Charleen [email protected] Université Laval

Salinas Patricia [email protected] University College London

Samartzis Dimitris [email protected] University of Athens

Sanchez-Huertas Carlos

[email protected] CRBM (CN-RS-UMR 5237)

Sar Shalom Hadas [email protected] Weizmann Institute of Science

Schmucker Dietmar [email protected] VIB and KU Leuven

Schulz Rouven [email protected] IST AustriaSeiradake Elena [email protected] University of

OxfordSergaki Maria Christina

[email protected] IMP

Siegert Sandra [email protected] IST Austria

Sinclair-Wilson Alexander

[email protected] ENS

Skarlatou Sophie [email protected] Max-Delbrueck-Center for Mo-lecular Medicine

Slepecka Olivia [email protected] IST Austria

Stoeckli Esther [email protected] University of Zurich



124

Name Email Address AffiliationStogsdill Jeff [email protected] Duke UniversityStreicher Carmen [email protected] IST AustriaSudakevitz Reut [email protected] The Hebrew Uni-


Surala Michael [email protected] University of Vienna

Suter Tracey [email protected] Brown UniversitySuzuki Takashi [email protected] Tokyo Institute of

TechnologyTripathy Ratna [email protected] IMPTulloch Alastair [email protected] Brown UniversityUrwyler Olivier [email protected] University of

ZurichVan Battum Eljo [email protected] UPMC - Institut de

la Vision Van de Haar Lieke [email protected] UMC UtrechtVan Rossum Danielle [email protected] UMC Utrecht

Verhagen Marieke [email protected] UMC UtrechtVerheijen Mark [email protected] UMC UtrechtVigouroux Robin [email protected] UPMC - Institut de

la VisionWeth Franco [email protected] Karlsruhe Institute

of TechnologyWilson Steve [email protected] University College

LondonWright Kevin [email protected] Vollum Institute, Wright Rebecca [email protected] Nature Neu-

roscienceYaron Avraham [email protected] Weizmann

Institute of Science



Notes

126

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