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of Eph/ephrin signaling in the developing cortex.

doi:10.1016/j.ijdevneu.2012.03.286

P.P. Kale, V. Addepalli / Int. J. D

eference

auger, S., et al., 2003. Phox2b controls the development of peripheral chemorecep-tors and afferent visceral pathways. Development 130, 6635–6642.

attyn, A., Morin, X., Cremer, H., Goridis, C., Brunet, J.-F., 1999. The homeobox genePhox2b is essential for the development of autonomic neural crest derivatives.Nature 399, 366–370.

attyn, A., Hirsch, M.-R., Goridis, C., Brunet, J.-F., 2000. Control of hindbrain motorneuron differentiation by the homeobox gene Phox2b. Development 127,1349–1358.

oi:10.1016/j.ijdevneu.2012.03.282

etermining the molecular signature of visceral neurons

. Coppola ∗, F. D’Autréaux, J.F. Brunet

Institut de biologie de l’école normale supérieure, Paris, France

The transcription factor (TF) Phox2b is required for the dif-erentiation of several classes of neurons. In contrast to mosteuronal-type specific TFs, which are expressed in discrete butnrelated types of neurons, the expression of Phox2b matchestrikingly well with a coherent set of neurons, defined by their con-ectivity and consequently function: the visceral neurons, afferentnd efferent, that connect the cardio-vascular, respiratory andigestive organs to the central nervous system. The use of theame transcription factor to specify all visceral neurons suggestshat, downstream of their common determinant and upstream ofheir common function, all visceral neurons share a core geneticrogram that we have set out to define through intersectional tran-criptomics. We are comparing the transcriptome of several classesf visceral neurons sorted ex vivo from embryos expressing YFPollowing the action of a Phox2b::Cre (enteric neurons, vagal gan-lionic neurons, and neurons of the nucleus of the solitary tract)nd looking for genes found in common, from which we will elim-nate ubiquitous, pan-neuronal or regional genes by comparison

ith YFP-neurons from the dorsal hindbrain of the same embryos.

oi:10.1016/j.ijdevneu.2012.03.284

GA enhanced cerebral uptake of intranasally deliveredmmunotherapeutics in Alzheimer’s transgenic mouse model

eelima B. Chauhan a,b,∗, Francesca Davis a,b, Balwantsinh C.hauhan c

Department of Pediatrics, Children’s Hospital of the University of Illi-ois, University of Illinois at Chicago, Chicago, IL, United StatesNeuroscience Research, Jesse Brown VA Medical Center, Chicago, IL,nited StatesDepartment of Biopharmaceutical Sciences, Roosevelt University,chaumburg, IL, United States

-mail address: nchauhan@uic.edu (N.B. Chauhan).Alzheimer’s disease (AD) is the 6th leading cause of death

n United States afflicting >5 million Americans and >16 mil-ion people worldwide. This number is estimated to triple byhe middle of the century if effective treatments are not discov-red. Current treatments for AD are mainly symptomatic. Effectiveisease-modifying treatments are needed that would eliminatehe cause (�-amyloid or A�) rather than the symptoms of theisease. Although A� immunotherapy has demonstrated promis-

ng therapeutic potential, it awaits the challenge of overcominglood–brain–barrier (BBB) limitations to allow greater influx of

nti-A� antibody into the brain. In that regard, the intranasal routef drug administration is a non-invasive and practical approach thatypasses the BBB and systemic adversities, to deliver immunother-peutics directly to the brain. This investigation was undertaken to

uroscience 30 (2012) 640–671 657

maximize the efficacy of intranasal passive immunization by usinga plant lectin called Wheat Germ Agglutinin (WGA) as a novel vehi-cle/carrier to exploit the active endocytic uptake preference andnasal mucosa-like composition of WGA that would effectively tar-get delivery of immunotherapeutics to the brain. This is the firstreport showing enhanced uptake of anti-A� antibody into the brainwith the use of WGA as an efficient carrier tested in Alzheimer’s5XFAD model. Given the lack of availability of disease modifyingtreatment(s) for Alzheimer’s disease, this investigation validatesthe use of WGA as a novel vehicle for enhancing intranasal passiveimmunization in Alzheimer’s disease that has a great potential ofbeing translated to human clinical trials.

doi:10.1016/j.ijdevneu.2012.03.285

Ephrin-B1 maintains apical anchorage of neural progenitorsthrough inhibition of ARF6

D.N. Arvanitis 1,2, A. Béhar 1,2, P. Tryoen-Tóth 3, J.O. Bush 4,5, T.Jungas 1,2, N. Vitale 3, A. Davy 1,2,∗

1 Centre de Biologie du Développement, CNRS, 118 Route de Narbonne,Bât 4R3, 31062 Toulouse cedex 9, France2 Université de Toulouse, UPS, F-310623 Département Neurotransmission et Sécrétion Neuroendocrine, Insti-tut des Neurosciences Cellulaires et Intégratives, CNRS UPR-3212,Université de Strasbourg, 5 rue Blaise Pascal, 67084 Strasbourg, France4 Department of Developmental and Regenerative Biology, Mt. SinaiSchool of Medicine, New York, NY 10029, USA5 Department of Cell and Tissue Biology and Program in Craniofacialand Mesenchymal Biology, University of California San Francisco, SanFrancisco, CA 94143-0442, USA

Neural progenitors are polarized cells whose apical process isthe site of cell–cell and cell–extracellular matrix adhesion eventsthat are essential to maintain the integrity of the developing cortex.These cell adhesion events are regulated during neurogenesis, yet,the mechanisms underlying this regulation remain poorly under-stood. Herein, we show that ephrin-B1, a cell surface protein thatis required for the maintenance of neural progenitors, is needed tomaintain apical anchorage of these cells at the ventricular surface.We show that EfnB1 deficient embryos exhibit cytoarchitecturedefects including alterations of the radial glia scaffold and abnor-mal neuronal migration. We demonstrate that ephrin-B1 influencesanchorage of neural progenitors by regulating ARF6 activity whichin turn modulates integrin-beta1 apical localization. Interestingly,our study shows that ephrin-B1 controls anchorage of neural pro-genitors by distinct molecular mechanisms to those required forthe maintenance of cell fate. Our results provide evidence for animportant role for ephrin-B1 in coupling cell morphology and cellfate in neural progenitors, thus emphasizing the complex function