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Bio 3411
Lecture III. Nervous System Embryology
September 5, 2012
Reading
Lecture III. Nervous System
Embryology
NEUROSCIENCE:
5th ed, pp. 477-506
NEUROSCIENCE:
4th ed, pp. 545-575
Bio 3411
Wednesday
September 5, 2012
September 5, 2012
Lecture III. Nervous System
Embryology
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Summary from Lecture II
Biology
Brain Diseases
•  Interfere with brain functions as heart disease
•  Understanding the brain is THE major question
interferes with the circulation.
•  Many diseases have a strong genetic component.
in biology and science.
•  Prevalence is high: ≈ 15 - 30% of the population.
•  Is it possible for the brain to understand itself?
•  Cost is high: >> $2+ Trillion/year in care, lost income,
social services, etc., in the US.
•  The brain like any organ has functions: input,
•  Impact (personal, family, societal) is persistent,
output, “thought”, communication.
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Lecture III. Nervous System
Embryology
pervasive, enormous, incalculable.
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Embryology
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Developmental Neurobiology
Issues for thought
Major scientific challenge.
Neurons (=nerve cells) ≈ 100 Billion
•  To understand the normal construction and
operation of the embryonic (and adult)
nervous system.
[the number of stars in our galaxy – the Milky Way!!]
Synapses (=clasp) 1/1,000,000th of all stars & planets
in the universe/person
•  To understand human neuronal diseases,
and possible ways to repair and renew
the nervous system.
[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
•  To understand neuronal plasticity, and
learning and memory.
genome are expressed only in Brain
[70% of the balance are also expressed in the nervous system; the total is 85% of
•  To understand the evolutionary diversification
of nervous systems.
the genome]
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Embryology
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Embryology
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Bio 3411
Lecture III. Nervous System Embryology
September 5, 2012
Major Questions
Development proceeds by progressive
developmental restrictions
1. Origins: Where do neurons come from?
pluripotent, stem cell
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?
differentiated
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Embryology
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Embryology
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Constructing a Nervous System
Developmental Restrictions may be:
EGG
1) Genetic (programmed by genes) or
2) Epigenetic (determined by environment)
Sort
Proliferate
pluripotent, stem cell
Shape
Specify
genetic
environmental
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differentiated
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Embryology
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Axons &
Synapses
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BRAIN
Cell
Death &
Life Experiences
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Embryology
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Vertebrate Embryology
(Frog)
• Egg – Blastula
An oocyte contains positional information (cytoplasmic
determinants) contributed maternally. Some maternal
RNAs are not uniformly distributed throughout the egg.
• Germ bands and cell types.
The first informational axis is intrinsic to oocyte!
Embryology
• Body axes.
Animal
• Folding, involutions and morphogenic
movements.
• Origin, migration and differentiation of
neurons.
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Lecture III. Nervous System
Embryology
Vegetal (yolk)
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Embryology
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Bio 3411
Lecture III. Nervous System Embryology
September 5, 2012
The point of entry of the sperm determines a second
positional axis, ventral (entry point) and dorsal
(opposite to entry point).
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
Cortical
granules
Sperm
entry point
Animal
Sperm
entry point
Cortical Rotation mixes
cytoplasmic determinants
and creates the
dorsal-ventral axis.
Ca+2
Vegetal (yolk)
Animal
Gray Crescent
(future blastopore)
Ventral
Vegetal (yolk)
Dorsal
future Nieuwkoop Center
Vegetal (yolk)
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Embryology
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Embryology
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Cortical Rotation redistributes maternal
cytosolic determinants that are partitioned
in different dividing embryonic cells
Gray Crescent Formation in Xenopus
Gray
Crescent
Nieuwkoop
Center
Courtesy of Jeffrey Hardin
University of Wisconsin
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Embryology
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Embryology
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Fate Mapping the Blastula:
3 Major Spatial Axes Formed by
Gradients of Signaling Molecules
Early Cell Divisions in Amphibians Generate a Blastula
(Animal)
(Ventral)
blastomere
blastocoel
Blastula
future
Blastopore
Site of
sperm entry
(Dorsal)
(Vegetal)
1. Animal/Vegetal (Maternal Determinants)
2. Dorsal/Ventral (Sperm Entry, Cortical Rotation)
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Embryology
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Embryology
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Fate Mapping the Blastula:
3 Major Spatial Axes Formed by Gradients of Signaling Molecules;
Nieuwkoop Center Induces the Spemann Organizer
(Anterior)
Fate Map of the Blastula:
3 Principle Germ Bands (Layers) Generated
Ectoderm
(Skin, Neurons)
(Anterior)
(Animal)
(Posterior)
(Posterior)
(Ventral)
Spemann
Organizer
Blastopore
Blastopore
(Dorsal)
Mesoderm
Nieuwkoop
Center
(Notocord, Muscle,
Kidney, Bone, Blood)
(Vegetal)
1. Animal/Vegetal (Maternal Determinants)
2. Dorsal/Ventral (Sperm Entry, Cortical Rotation)
Endoderm
(Lining of Gut, Lungs,
Placenta in Mammals)
3. Anterior/Posterior (Spemann Organizer)
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Embryology
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Gastrulation of the Amphibian Blastula A & B:
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Embryology
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Gastrulation of the Amphibian Blastula C & D:
“tissue origami” by large-scale cellular migrations and morphogenesis
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“tissue origami” by large-scale cellular migrations and morphogenesis
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Embryology
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Gastrulation of Xenopus Blastula:
3-D Microscopic (Confocal) Reconstruction
Gastrulation of the Amphibian Blastula E & F:
“tissue origami” by large-scale cellular migrations and morphogenesis
(Ewald, et al., 2004)
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Embryology
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Embryology
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Lecture III. Nervous System Embryology
September 5, 2012
Gastrulation and neurulation in Xenopus
(Courtesy of Jeffrey Hardin, University of Wisconsin)
Endoderm and Mesoderm
Involute with Gastrulation
Mesoderm underlies (Neuro)Ectoderm,
And induces the neural plate
Neural plate
(apposition of
different
germbands/
layers)
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Blastopore
and
yolk plug
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Embryology
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Embryology
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Early cell divisions in the Zebrafish embryo
(Courtesy of Paul Myers, University of Minnesota)
Neurulation
Ant
Closure of the neural tube.
Post
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Embryology
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Neurulation
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Origin of Floor Plate and Neural Crest
D
Formation of Neural Crest Cells
(makes PNS, endocrine cells,
pigment cells, connective tissue).
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Neural Crest
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Embryology
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Cephalization and Segmentation of the Neural Tube
Origin of Floor Plate and Neural Crest
Neural Crest
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Embryology
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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
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.
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The earliest born neurons are found closest to
the ventricular surface (thymidine pulse-chase
labeling of dividing cells).
(Rakic, 1974)
(Nadarajah, et al., 2002)
(Cepko and Sanes
Labs, 1991)
(Nector, et al., 2001)
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Embryology
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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):
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Embryology
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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)
a) Blastula flattens into
the inner cell mass.
3. Telolecithal eggs
(reptiles, birds, fish):
b) Endodermal cells
form the trophoblast
and placental structures.
(epiboly)
(blastodisc)
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Embryology
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Embryology
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Bio 3411
Lecture III. Nervous System Embryology
September 5, 2012
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).
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.
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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Embryology
What this Lecture was About (cont):
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Embryology
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Central Aspects of Embryogenesis
Embryogenesis (cont.):
1. Oocyte possess maternal cytoplasmic determinants.
2. Fertilization triggers calcium influx, and creates
dorsal-ventral axis by cortical rotation.
7. Apposition of future mesoderm with neuroectoderm
induces the neural plate.
3. Cell divisions, synchronous at first, then asynchronous.
4. Blastula created. (“Hollow” ball of cells)
8. Neurulation. (Lateral neural folds bend over the
midline and fuse into the neural tube.)
6. Germ bands (ectoderm, mesoderm, endoderm) created
by molecular signals along the Animal/Vegetal axis.
9. Neural crest cells derived from leading edge of neural
folds, migrate into somites to form the PNS.
5. Gastulation. (Involution of superficial cells through
the blastopore).
10. Segmentation, anterior enlargement (cephalization),
cortical development and spinal specification.
6. Anterior-posterior axis created by Spemann organizer.
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Embryology
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Embryology
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