ed, pp. 477-506 Lecture III. Nervous System Embryology … Embryolog… · Bio 3411 Lecture III. Nervous System Embryology September 5, 2012 3 Fertilization triggers an influx of

Bio 3411 Lecture III. Nervous System Embryology

September 5, 2012

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Lecture III. Nervous System Embryology

Bio 3411 Wednesday

September 5, 2012

Reading

NEUROSCIENCE: 5th ed, pp. 477-506 NEUROSCIENCE: 4th ed, pp. 545-575

September 5, 2012 Lecture III. Nervous System Embryology

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Biology

•  Understanding the brain is THE major question

in biology and science.

•  Is it possible for the brain to understand itself?

•  The brain like any organ has functions: input,

output, “thought”, communication.

Summary from Lecture II


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Brain Diseases •  Interfere with brain functions as heart disease

interferes with the circulation. •  Many diseases have a strong genetic component. •  Prevalence is high: ≈ 15 - 30% of the population.

•  Cost is high: >> $2+ Trillion/year in care, lost income, social services, etc., in the US.

•  Impact (personal, family, societal) is persistent, pervasive, enormous, incalculable.


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Issues for thought Neurons (=nerve cells) ≈ 100 Billion [the number of stars in our galaxy – the Milky Way!!]

Synapses (=clasp) 1/1,000,000th of all stars & planets in the universe/person [less than the total of human synapses of people living in the St.L area!!]

vs Genes 50% of ≈ 20,000-25,000 genes in the human genome are expressed only in Brain [70% of the balance are also expressed in the nervous system; the total is 85% of the genome]


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Major scientific challenge. •  To understand the normal construction and operation of the embryonic (and adult) nervous system. •  To understand human neuronal diseases, and possible ways to repair and renew the nervous system. •  To understand neuronal plasticity, and learning and memory. •  To understand the evolutionary diversification of nervous systems.

Developmental Neurobiology


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1. Origins: Where do neurons come from? 2. Identity: How does a cell become a neuron? 3. Specificity: How does a neuron make the right

connections? 4. Plasticity: Does experience modulate the above?

September 5, 2012

Major Questions


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pluripotent, stem cell

differentiated

Development proceeds by progressive developmental restrictions


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Developmental Restrictions may be: 1) Genetic (programmed by genes) or 2) Epigenetic (determined by environment)

pluripotent, stem cell

differentiated

genetic

environmental


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Constructing a Nervous System

Axons & Synapses

Cell Death &

Life Experiences

Proliferate Sort

Shape Specify

September 5, 2012

EGG

BRAIN


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Embryology • Egg – Blastula

• Germ bands and cell types.

• Body axes.

• Folding, involutions and morphogenic movements.

• Origin, migration and differentiation of neurons.


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Vertebrate Embryology (Frog)

An oocyte contains positional information (cytoplasmic determinants) contributed maternally. Some maternal RNAs are not uniformly distributed throughout the egg. The first informational axis is intrinsic to oocyte!

Animal

Vegetal (yolk)


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September 5, 2012

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Fertilization triggers an influx of calcium, that sweeps across the egg. This causes rapid release of cortical granules to form the fertilization envelope, blocking polyspermy.

Animal

Vegetal (yolk)

Sperm entry point

Ca+2

Cortical granules


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The point of entry of the sperm determines a second positional axis, ventral (entry point) and dorsal (opposite to entry point).

Cortical Rotation mixes cytoplasmic determinants and creates the dorsal-ventral axis.

Animal

Vegetal (yolk)

Sperm entry point

Animal

Vegetal (yolk)

Ventral

Dorsal

Gray Crescent (future blastopore)

future Nieuwkoop Center


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Gray Crescent Formation in Xenopus

Courtesy of Jeffrey Hardin University of Wisconsin


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Cortical Rotation redistributes maternal cytosolic determinants that are partitioned in different dividing embryonic cells

Gray Crescent

Nieuwkoop Center


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Early Cell Divisions in Amphibians Generate a Blastula

Blastula blastocoel blastomere


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Fate Mapping the Blastula: 3 Major Spatial Axes Formed by Gradients of Signaling Molecules

(Ventral)

(Dorsal)

future Blastopore

(Vegetal)

(Animal)

Site of sperm entry

1. Animal/Vegetal (Maternal Determinants) 2. Dorsal/Ventral (Sperm Entry, Cortical Rotation)


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September 5, 2012

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Fate Mapping the Blastula: 3 Major Spatial Axes Formed by Gradients of Signaling Molecules;

Nieuwkoop Center Induces the Spemann Organizer

1. Animal/Vegetal (Maternal Determinants) 2. Dorsal/Ventral (Sperm Entry, Cortical Rotation) 3. Anterior/Posterior (Spemann Organizer)

Blastopore

Spemann Organizer

Nieuwkoop Center

(Anterior)

(Posterior)


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Fate Map of the Blastula: 3 Principle Germ Bands (Layers) Generated

Blastopore

(Anterior)

(Posterior) (Ventral)

(Dorsal)

(Vegetal)

(Animal) Ectoderm (Skin, Neurons)

Mesoderm (Notocord, Muscle, Kidney, Bone, Blood) Endoderm

(Lining of Gut, Lungs, Placenta in Mammals)


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Gastrulation of the Amphibian Blastula A & B:

September 5, 2012

“tissue origami” by large-scale cellular migrations and morphogenesis


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Gastrulation of the Amphibian Blastula C & D:



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September 5, 2012

Gastrulation of the Amphibian Blastula E & F:



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Gastrulation of Xenopus Blastula: 3-D Microscopic (Confocal) Reconstruction

September 5, 2012

(Ewald, et al., 2004)


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September 5, 2012

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Blastopore and

yolk plug

Mesoderm underlies (Neuro)Ectoderm, And induces the neural plate

September 5, 2012

Endoderm and Mesoderm Involute with Gastrulation

Neural plate (apposition of different germbands/ layers)


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Gastrulation and neurulation in Xenopus (Courtesy of Jeffrey Hardin, University of Wisconsin)


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Early cell divisions in the Zebrafish embryo (Courtesy of Paul Myers, University of Minnesota)


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Neurulation

Closure of the neural tube.

Ant

Post


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Neurulation

D

V

Formation of Neural Crest Cells (makes PNS, endocrine cells, pigment cells, connective tissue). Neural Crest


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Origin of Floor Plate and Neural Crest


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Origin of Floor Plate and Neural Crest

Neural Crest


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Cephalization and Segmentation of the Neural Tube


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Cortical Development: Laminar structure of the cortex is constructed from the inside-out

Neurons are born in the ventricular layer and migrate radially along glia to their

differentiated adult cortical layer.

The earliest born neurons are found closest to the ventricular surface (thymidine pulse-chase

labeling of dividing cells).

(Rakic, 1974)


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Labeling of Single Precusors Reveal Shared Clonal Origins of Radial Glia and Neurons;

and Direct Visualization of Radial and Tangential Migrations

(Nadarajah, et al., 2002)

(Nector, et al., 2001)

(Cepko and Sanes Labs, 1991)


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The amount of yolk determines the symmetry of early cleavages and the shape of the blastula

1.  Isolecithal eggs (protochordates, mammals):

2. Mesolecithal eggs (amphibians):

3. Telolecithal eggs (reptiles, birds, fish):

(blastodisc)

(epiboly)


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a) Blastula flattens into

the inner cell mass. b) Endodermal cells

form the trophoblast and placental structures.

Mammalian eggs have no yolk, so early divisions resemble isolecithal eggs (protochordate-like). However, later stages resemble the blastodisc of telolecithal eggs (reptile/bird/fish-like)


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September 5, 2012

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What this Lecture was About 1. Three germbands (layers), ectoderm (skin and neurons), mesoderm (muscle, blood and internal organs) and endoderm (lining of the gut). 2. Development proceeds from pleuripotency (stem cells) to the differentiated state (adult neuron). 3. Neuronal induction requires specific contact between groups of cells; embryonic morphogenesis allows this to occur. 4. Positional information is created early by asymmetric distribution of molecules. These form axes (Animal/Veg, D/V, Ant/Post) that guide the movement of embryonic cells.


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What this Lecture was About (cont): 5. Guideposts: a) Fertilization/Cortical Rotation. b) Blastula (hollow ball of cells). c) Gastrulation (inside-out involution of surface cells to the interior, through the blastopore). d) Neurulation (neural tube formation). e) Segmentation/Cephalization. f) Birth of neurons from the ventricular zone. Radial, then tangential migration to final destination.


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Central Aspects of Embryogenesis 1. Oocyte possess maternal cytoplasmic determinants. 2. Fertilization triggers calcium influx, and creates dorsal-ventral axis by cortical rotation. 3. Cell divisions, synchronous at first, then asynchronous. 4. Blastula created. (“Hollow” ball of cells) 6. Germ bands (ectoderm, mesoderm, endoderm) created by molecular signals along the Animal/Vegetal axis. 5. Gastulation. (Involution of superficial cells through the blastopore). 6. Anterior-posterior axis created by Spemann organizer.


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Embryogenesis (cont.): 7. Apposition of future mesoderm with neuroectoderm induces the neural plate. 8. Neurulation. (Lateral neural folds bend over the midline and fuse into the neural tube.) 9. Neural crest cells derived from leading edge of neural folds, migrate into somites to form the PNS. 10. Segmentation, anterior enlargement (cephalization), cortical development and spinal specification.


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END

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ed, pp. 477-506 Lecture III. Nervous System Embryology … Embryolog… · Bio 3411 Lecture III. Nervous System Embryology September 5, 2012 3 Fertilization triggers an influx of