Neuronal development

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Neuronal development

• Ursula Winzer-Serhan
• MSCI602
• February 2006

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Steps during neural development

• Neurogenesis
• Compartmentalization
• Neural differentiation
• Neural migration
• Axonal guidance
• Synaptogenesis

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Neural development in vertebrate embryo
Gastrulation "It is not birth, marriage, or
death, but gastrulation, which is truly the most
important time in your life Lewis Wolpert
(1986)
Blastula stage embryo with three germ layers,
first signs of invagination of dorsal blastopore
lip
Embryo in midgastrulation, involution of dorsal
mesoderm (organizer tissue).
Gastrula stage embryo Embryo at end of
gastrulation. The three germ layers have arrived
at their final destination
FIGURE 1 Blastula stage through neurulae,
highlighting gastrulation and neurulation.
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Organizing CentersRestricted specialized areas
that are crucial for the induction of area
specification

• Spemanns organizer (dorsoblastopore lip)
• Hensens node (similar to Spemanns org)
• Roofplate notochord become organizers
• secondary organizers
• Isthmic organizer (IsO)
• Anterior neural ridge (ANR)
• Cortical hem

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Organizer Transplant experiment
A region just above the blastopore lip
(mesodermal tissue) is excised transplanted to
ventral side of host.
The host embryo develops a secondary dorsal
axis, first evident by a secondary neural plate.
A section through a host embryo with two dorsal
axes Secondary dorsal axis contains the same
tissues as the primary dorsal axis, including a
nervous system. Note neural tissue was
derived from recipient cells, not donor cells.
Thus, the transplant had altered the fate of the
overlying cells
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Default model of neural induction. Balance
between agonists and antagonists!Importance of
inhibition as a developmental regulatory
mechanism.

• Expression of signaling factors
• Bone morphogenic protein (BMP), a TGF-ß-like PGF
  expressed in ectoderm on ventral side, inducing
  ectoderm to become epidermis.
• Organizer on the dorsal side releases inhibitors
  of the BMPs noggin, chordin, and follistatin,
  which diffuse into the ectoderm on the dorsal
  side, block the effects of BMPs, and allow neural
  tissue to form.

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Signaling pathway involving BMPs
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Signaling pathway involving BMPs

• Large family of polypeptide growth factors (PGF)
  related to transforming growth factor-ß (TGF-ß)
  BMP, activin, and GDF group members.
• Heterodimer receptors, with type I type II
  subunits, cytoplasmic domains with
  serine/theronine kinase activity.
• Dimerization after binding of a TGF-ß-like PGF
  starts signal transduction pathway Activation of
  cytoplasmic proteins (SMADs), which translocate
  to nucleus to activate expression of downstream
  target genes.
• Inhibitory mechanisms regulate signaling
• Extracellular proteins such as chordin, tolloid,
  and twisted gastrulation interact with the
  BMP-like ligands, regulating their diffusion
  through the extracellular milieu and their
  ability to bind receptor
• Cell surface proteins such as BAMBI inhibit
  signaling by binding up BMPs but failing to
  transduce a signal.
• Inhibitory SMADs poison the signal transduction
  pathway.

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Neurulation
The neural plate forms after gastrulation is
completed.
The neural tube narrows along its
medial-lateral Axis. The plate begins to role
into a tube. The cells at the midline produce a
medial hinge point (MHP).
As the tube forms and segregates into the embryo,
neural crest cells emigrate from the dorsal
aspect of the neural tube.
G.C. Schoenwolf
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Steps during neural development

• Neurogenesis
• Compartmentalization
• Neural differentiation
• Neural migration
• Axonal guidance
• Synaptogenesis

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Early neural patterningEstablishment of AP Axis

• Head and tail organizer release factors which
  create a gradient.

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AP polarity of vertebrate CNS

• Head organizer becomes precordal mesoderm (PME)
  underneath prechordal plate
• Tail organizer becomes notochord and somites,
  underneath epichordal neural plate

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Tail organizer FGF, WNT, RA BMP inhibitors Are
posteriorizing signaling molecules
Head organizer BMP Inhibitors Cordin Noggin,
Wnt inhibitors Cerberus, Dickkopf frzb1 to
"anteriorize" neural tube
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Patterning of the brain and spinal cord through
compartmentalization
Melton, Iulianella, Trainor, 2004
Regional patterning Forebrain (FB), Midbrain
(MB), Hindbrain (HB) and Spinal cord (SC).
Graded Wnt signaling functions along the entire
length of the neuraxis inducing progressively
more posterior neural fates. Hox genes play
important roles in establishing regional cell
identity. This is achieved via opposing gradients
of RA and FGF signaling.
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Hox gene expression domains in the CNS
Nested domains of homeotic genes along the AP
axis of the Drosophila and mouse CNS. Hox genes
specify a positional value along the AP axis,
which is interpreted differently in fly and mouse
in terms of downstream gene activation, resulting
in neural structure after Hirth et al., (1998).
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Compartmental organization of hindbrain into
rhombomeres
Stage 8-9 Genes are expressed in alternate
stripes that correspond with presumptive Rhombome
res.
Stage 9-10 Restriction of movement of
mitotic Precursor cells across interfaces.
Stage 13 The interfaces between Rhombomeres
acquire molecular and Morphological
specialization marked by distinct boundaries.
Example of odd/even gene expression in
Drosophila in situ localization of the achaete
transcript
From Skeath et al, 1992.
Julie E. Cooke, Cecilia B. Moens, 2002
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Stages in the compartmental organization of
rhombomeres.
Genes such as Krox20 and EphA4 (blue) and
ephrin-B2 (pink) are expressed in alternate,
fuzzy-edged stripes (left). Subsequently,
restriction to the movement of mitotic precursor
cells occurs at the interfaces between newly
formed rhombomeres, which are now sharply
defined, and marked by increased intercellular
spaces. (right)
Sharpening of boundaries and cell lineage
restriction occur through the interaction of Eph
and ephrin molecules. Data from Fraser et al.
(1990).
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Regional specification in the developing brain
Five-vesicle state
Three-vesicle state of a chick embryo
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Dorsal Ventral pattern Notochord as organizer
Left During development, the floor plate (red)
develops above the mesodermal notochord (n) and
motor neurons (yellow) differentiate in adjacent
ventrolateral region of the neural tube. Center
Grafting a donor notochord (n') alongside the
folding neural plate results in formation of an
additional floor plate and a third column of
motor neurons. Right Removing the notochord
from beneath the neural plate results in the
permanent absence of both floor plate and motor
neurons in the region of the extirpation. Pax6
expression (blue) extends through the ventral
region of the cord.
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Sonic-hedge-hog expression by notochord floor
plate, control of ventral patterns
Shh activity in the ventral neural tube (blue
dots) is distributed in a ventral-high,
dorsal-low profile within the ventral neural
epithelium. 5 classes of neurons are generated in
response to graded Shh signalling
T.M. Jessell, 2000
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Model for ventral neural patterning by SHH.
Left Graded SHH signaling from the ventral pole
induces expression of some homeobox genes (e.g.,
Nkx2.2, Nkx6.1) and represses existing expression
of others (e.g. Pax6, Dbx2). Center
Cross-repressive interactions between pairs of
transcription factors sharpen mutually exclusive
expression domains. Right Profiles of homeobox
gene expression define progenitor zones and
control neuronal fate. After Briscoe and Ericson,
(2001).
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Regulation of DV pattern in the telencephalon by
SHH.
Cross section of mouse telencephalon at early
(left) and later (right) stage. SHH produced in
the ventral midline region controls development
of basal ganglia primordia and medial and lateral
ganglionic eminences (MGE, LGE). First, ventral
SHH induces MGE gene expression SHH (partly
produced by the MGE) induces LGE gene expression
later.
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The neural tube, shown here for a mouse, is
subdivided into four longitudinal domains the
floor plate, basal plate, alar plate, and roof
plate. Motor neurons are derived from the basal
plate.
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Steps during neural development

• Neurogenesis
• Compartmentalization
• Neural differentiation
• Intrinsic factors
• Extrinsic factors
• Determine cell fate
• Neural migration
• Axonal guidance
• Synaptogenesis

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Schematic diagram of an idealized embryo in cross
section showing pathways of neural crest
migration in trunk and derivatives formed.
Neural crest cells migrate along two primary
pathways dorsally under the skin, ventrally
through the sclerotome. Dorsal migrating cells
form pigment cells, ventrally migrating cells
form dorsal root and sympathetic ganglia, Schwann
cells, and cells of the adrenal medulla.
Drawn by Mark Selleck.
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Trunk neural crest cells migrate in a segmental
fashion.
A) Schematic diagram demonstrating that neural
crest cells migrate through the sclerotomal
portion of the somites, but only through the
rostral half of the sclerotome. B) In
longitudinal section, neural crest cells (green)
can be seen migrating selectively through the
rostral half of each somitic sclerotome (S).
From Bronner-Fraser (1986).
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Differentiation of cranial neural crest
cellsTGF-ß Regulates Expression of
Transcription Factorsto Determine the Fate of
Cranial Neural Crest Cells
CNC cells give rise to an array of tissue types
odontoblasts, chondroblasts, osteoblasts, neural
tissues, such as sensory neurons and cranial
nerve ganglia etc. Both ectoderm and endoderm of
the branchial arch provide signaling instructions
for the fate specification of these progenitor
cells. Chai et al., 2003
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Neuroblast differentiation Series of GF and
transcriptional regulators affecting neurogenesis
of neural crest progenitors.
Neural crest cells can be identified by the
expression of FoxD3 and SOX10. Progenitor cells
differentiate into sympathetic, parasympathetic,
enteric, or sensory neurons dependent upon
instructive signals encountered at or near the
time of egress from the neural tube. Extrinsic
cues encountered during migration or at sites
where neural crest-derived cells differentiate
influence patterns of gene expression.
From Howard, 2004
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Specification and differentiation of peripheral
autonomic neurons are dependent upon the
interplay between cell extrinsic and cell
intrinsic factors.
Initial instructive cues from the neural tube
influence neural crest cells to respond to BMPs.
Induction of Phox2b and MASH1 is followed by the
induction of HAND2 and Phox2a resulting in
expression of pan-neuronal (SCG10, NF) and cell
type-specific (TH, DBH, ChAT, VAChT) genes.
M.J. Howard, 2004
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Transmitter switching by target-derived factors.
A) All sympathetic neurons start as
noradrenergics. Some innervate the sweat glands
and switch their transmitter phenotype as the
sweat gland matures and stop tyrosine hydroxylase
and start choline acetyltransferase synthesis.
B) The adrenergic-to-cholinergic switch can be
prevented by replacing sweat gland-rich targets
with tissue usually receiving adrenergic
innervation. Conversely, an adrenergic-to-choliner
gic switch can be accomplished by transplanting
foot pad tissue onto hairy skin, which is usually
innervated by adrenergic sympathetic neurons. C)
Factors such as LIF and CNTF, found in target
tissues can influence neurotransmitter choice in
cultured sympathetic neurons causing cells that
would differentiate as adrenergic neurons to
become cholinergic.
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Neuronal Glial Lineages are derived from common
progenitors
A) 2 identified neuroglioblasts in the Drosophila
neuroblast map (see Fig 7A). B) Separation of
neuronal and glial sublineages in progenitor 6-4.
The glial regulatory protein, Gmc, is expressed
in 6-4. When this cell divides into two equally
sized daughter cells, 6-4 G and 6-4 N, the
Inscuteable complex and Miranda segregate Gmc
into 6-4 G, which thereby becomes specified as
glioblast. C, D) The MNB neuroblast produces
both glial cells and neurons. The engrailed gene,
which encodes a homeodomain transcription factor,
is required for glial sublineage. When en
function is reduced by injecting antisense
oligonucleotides, MNB forms only neurons (D).
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Neuronal lineage determined by intrinsic
factorsMouse Numb is inherited asymmetrically

• Asymetrical division of cells.
• Dividing pair of daughter precursor cells
  uniformly stained for a proneural gene.
• Only one daughter cells inherits the numb protein
  (green).
• Double labeling for proneuronal and numb gene
  (yellow).
• Asymmetrical distribution in neuronal progenitor
  cells from cortex, neural crest, and spinal cord.

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Neurons are born Neurogenesis

• Neurons are born in the ventricular zones close
  to the brain ventricles
• Neurons are born mostly prior to birth
• Birth dating studies can determine the time of
  the last cell division
• 3Hthymidine or BrdU labeling to determine
  birthdate of the neurons
• Glia cells proliferate throughout life

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Cortical neurons are born consecutively
Neurogenetic timetable for the neocortex, based
on long-survival 3Hthymidine auto- radiography
in the rat. SA Bayer J Altman, 1993
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Development of the cerebral cortex.
The ventricular zone (VZ) contains the
progenitors of neurons and glia. The first
neurons to be generated establish the preplate
(PP) their axons, as well as ingrowing axons
from the thalamus, establish the intermediate
zone (IZ). Neurons of cortical layers IIVI
establish the cortical plate (CP), which splits
the preplate into the marginal zone (MZ), or
future layer I, and the subplate (SP), a
transient population of neurons.At the end, six
cortical layers are visible overlying the white
matter (WM) and the subplate has largely
disappeared. Neural precursors in the
subventricular zone (SVZ) continue to generate
neurons that migrate rostrally into the olfactory
bulb, even during postnatal life.
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Laminar fate determination in the cerebral
cortex.

• Morphogenesis of the mammalian cerebral cortex.
  Neural precursors are born in the ventricular
  layer and migrate away from the ventricular
  surface, following tracks provided by radial
  glial cells. The first born cells are the
  Cajal-Retzius neurons (left). Later born neurons
  accumulate in a dense matrix of cells, the
  cortical plate (middle). In this plate, neurons
  are ordered by birth date in such a way that
  older neurons (magenta) remain in deep layers,
  and younger neurons (blue) migrate through the
  deep layers to attain a superficial position
  (right).
• B) If ventricular cells from young donors (which
  would become deep cells) are transplanted into an
  old host, they adapt to their new environment and
  develop as superficial neurons (arrow).
• C) In converse heterochronic transplantation (old
  donor to young host), transplanted ventricular
  cells maintain their laminar fate and become
  superficial neurons.
• D) Layer 4 neurons transplanted into older brains
  switch their fate so that it is appropriate for
  the upper layer neurons.
• E) When layer 4 neurons are transplanted into
  younger hosts, they end up in layers 4 and 5, but
  not layer 6.

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Is there neurogenesis in the adult Brain?

• Yes there is, in the
• Dentate gyrus
• Olfactory bulb

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Neurogenesis in adult rat hippocampus
One day after BdDU injection
4 weeks after BrDU injection
Neuronal marker Neu plus BrDU labeled cells
F. Gage, Salk, San Diego
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Steps during neural development

• Neurogenesis
• Compartmentalization
• Neural differentiation
• Neural migration
• Axonal guidance
• Synaptogenesis

40
After neurons are born, they migrate to their
final destinationsRadial migrationTangential
migration
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Radial migration along radial glia cells in the
developing CNS
Serial section electron microscopy Migrating
neurons in the intermediate zone are intimately
apposed to radial glial fibers (striped vertical
shafts, RF1-6), which extend short lamellate
expansions (LE) at a right angle to their main
axis. Nuclei (N) of migrating neurons are
elongated, and their leading processes (LP) are
thicker and richer in organelles than their
trailing processes (TP). Each leading process
extends several pseudopodial endings (PS).
Several cross sections through a migrating neuron
are shown (ad) migrating cell partially
encircles the shaft of the radial glial fiber and
these intimate contacts are continuous throughout
the length of the cell. OR, optic radiation, From
Sidman and Rakic (1973).
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Radial migration along radial glia in the
developing Cerebellum, Hippocampus and Cortex
In vitro migration of hippocampal neurons along
the process of astroglia cells from the
cerebellum. Neurons can migrate along a variety
of radial glia fibers.
Migrating neurons are apposed to glia Cells,
which guide them from the ventri- cular zone to
their final destination.
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Cortical neurons are migrating over long distances
Diagram of various trajectories taken by
migrating cortical cells co-generated at the same
embryonic day, but destined to settle in various
areas of the cortical plate. Some cells
generated in the neocortical neuroepithelium
migrate in the lateral cortical stream for four
or more days before reaching their target
destination.
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The role of the Reelin protein in cortical
development.
A) Reelin is expressed by Cajal Retzius cells in
the outer layer of the developing cortex. As
neurons migrate out along the glial fibers,
Reelin is proposed to organize the cortical
plate. B) Reelin binds to a receptor, VLDLR or
ApoER2 in the surface membrane, which leads to
downstream signaling via Dab1, resulting in
alterations in gene expression. In addition, Cdk5
phosphorylates cytoskeletal components such as
tau and neurofilaments, which may affect
organization of the cytoskeleton and properties
of migrating neurons. Procadherins act as
another class of reelin receptors.
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Players in the formation of the neuronal layers
of cerebral cortex.
Layer 1 (Cajal-Retzius cells, blue), secrete
Reelin. Cells migrate along the radial glia
(green) using genes that provide components of
the cytoskeleton (Lis1, Dcx, Filamin1, and
Cdk5/p35) or neuron-glia binding (Astn1, and
Integrin 3). Mutations in any of these genes
results in brain malformations.
ME Hatten, 2002
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Steps during neural development

• Neurogenesis
• Compartmentalization
• Neural differentiation
• Neural migration
• Axonal pathfinding
• Synaptogenesis

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Axonal growth cone
Karl H. Pfenninger
Movement of the growth cone is mediated by a
cytoskeletal lattice containing the motor
proteins actin and myosin. As the neurite extends
behind the moving growth cone, the microtubule
backbone of the neurite is constructed from
molecules of tubulin.
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Guidance of Axons by short- and long-range cues
Attractive or repulsive
Four types of mechanisms contribute to the
guidance of the growth cone Contact attraction,
chemoattraction contact repulsion,
chemorepulsion. Individual growth cones might be
"pushed" from behind by a chemorepellent,
"pulled" from in front by a chemoattractant, and
"hemmed in" by attractive and repulsive local
cues (cell surface or extracellular matrix
molecules).
Adapted from Tessier-Lavigne and Goodman (1996).
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Molecular guidance moleculesConserved families
of guidance molecules (A) and their receptors
(B).
Examples ? SLIT secreted proteins, control
midline repulsion, dual role, signaling through
roundabout receptors (Robo) ? Ephrins (A B)
membrane anchored, repellent and attractive
functions, receptors EphA, EphB ?Netrins and
their receptors ?Semaphorins 5 different
subfamilies characterized by a 500 aa semaphorin
domain, secreted and anchored. Cell Adhesion
Molecules ( N-CAM, L1 or Fasciclins
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Semaphorins example for dual function
Dual function
D) In the presence of NGF Sema III has a
repellent effect on neurite growth
E) In the presence of NT3, Sema III elicits
outgrowth of neurites (NT-3)
.
Secreted (subclass 2 3) or membrane bound
ligands (GPI anchored or transmembrane
domain) have Chemorepellent or chemoattractive
functions.
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Linkage of the actin cytoskeleton to a permissive
surface is required for forward advance.
Actin is polymerized at the leading edge of the
growth cone (right) and is swept toward the rear.
If the actin meshwork is not linked to cell
surface receptors that bind permissive molecules
on adjacent cell surfaces, the actin cycles from
front to rear but does not advance the growth
cone. If the actin meshwork is attached to these
receptors, the meshwork remains in place and
newly polymerized actin helps advance the leading
edge.
Modified from Lin et al.(1994).
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Ephrins Eph receptors
  Ephrin-expressing cell (top) interacting with
Eph-receptor expressing cell (bottom).
Ligandreceptor interactions (green) are dimeric
or oligomeric Ephephrin complexes. GPI,
glycosylphosphatidylinositol SAM, sterile alpha
-motif. Functions Vascular development Border
formation Cell migration Axon guidance Synaptic
plasticity
Klas Kullander1 Rüdiger Klein, 2002
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Projections from preplate guide thalamocortical
fibers
Top Preplate cells send out their axons towards
the internal capsule (red). Thalamic axons
project through the IC and meet cortical axons.
Right Handshake between thalamic and preplate
axons and precise topography of early
thalamicortical projections
Note Axons travel together (fasciculation) Axons
use preexisting projections Guidepost cells
show the way
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Steps during neural development

• Neurogenesis
• Compartmentalization
• Neural differentiation
• Neural migration
• Axonal guidance
• Synaptogenesis
• Example
• Neuromuscular junction

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Neuromuscular junction synapseAn
electronmicroscopic view
Pre- and postsynaptic membranes are highly
specialized. The nerve terminal is capped by a
Schwann cell and is situated in a shallow
depression of the muscle cell membrane
(postjunctional fold). ACh vesicles are
concentrated at the presynaptic site. Rapsyn,
neuregulin receptors and muscle specific kinase
are concentrated at the postsynaptic site.
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(No Transcript)
57
Agrin-mediated signaling
Motor neurons synthesize and release Agrin into
the synaptic basal lamina, where it acts to
maintain AChRs (green/yellow) at synaptic sites.
Agrin stimulates the clustering of synaptic
proteins including AChR, AChE, Rapsyn, Utrophin,
neuregulin1, NRG receptors. Before innervation,
AChRs (green) are spread diffusely over the
surface of the myotube. Release of agrin after
innervation results in the redistribution of
previously unclustered AChRs to synaptic sites,
adjacent to the nerve terminal.
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Synapse at the neuromuscular junction
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 Trans-synaptic protein interactions implicated
in synaptic contact/adhesion synapse
development Some players
Homophilic interactions The carboxy-terminal
cytoplasmic tails of -neurexin, neuroligin,
EphB2, ephrinB and SynCAM (synaptic cell-adhesion
molecule) bind to specific PDZ and
ZO-1-domain-containing proteins, which can
assemble large protein complexes that are
associated with the cell-surface membrane
protein. Zheng Li Morgan Sheng 2003
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Presynaptic and postsynaptic elements at
glutamatergic synapses. The PDZ-containing
protein PSD-95 binds to NMDA receptors, PICK-1
and GRIP, bind to AMPA receptors. Presynaptic
ßneurexin binds to postsynaptic Neuroligin which
is associated with NMDA receptors via PSD-95 to
align pre- and postsynaptic sites. Pre-synaptic
ephrinB binds to postsynaptic EphB2 receptors,
clustering NMDA receptors. EphB2 receptors bind
to PICK-1 GRIP linking NMDA and AMPA receptors.
Interactions between Narp AMPA receptors have
been established by in vitro binding and
immunoprecipitation experiments the importance
remains to be determined.
61
Rat hippocampal neuron in culture expressing
beta-Gal to visualize the dendrites, and
immunostained for beta-Gal (green) and PSD-95
(red), a protein enriched in postsynaptic
structures, the dendritic spines. Maria Morabito,
Ph.D.
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Synapse Elimination
The total number of synapses on ganglion cells in
the rat submandibular ganglion increases during
early postnatal life.
63
Innervation of individual neuromuscular junctions
(ovals on muscle fibers) by axonal branch
trimming.
Over the first several weeks of postnatal life,
rodent motor axons remove branches each
neuromuscular junction undergoes a transition
from innervation by multiple converging axons to
innervation by only one axon. The number of
muscle fibers innervated by an axon decreases
substantially 9axonal convergence decreases) and
all but one input is eliminated from each
fiber. This occurs by branch removal rather than
motor neuron death.
64
Time-lapse imaging of synapse elimination.
Two neuromuscular junctions (NMJ1 and NMJ2) in
vivo on postnatal days 7, 8, and 9 in a
transgenic mouse that expresses YFP in its motor
axons. The acetylcholine receptors at the muscle
fiber membrane are labeled red with rhodamine
tagged abungarotoxin in each muscle fiber. The
transition from multiple to single innervation of
NMJ1 as one axon, a sibling branch of the axon
that innervates NMJ2, undergoes atrophy and
appears to retract. The eliminated branch
terminates in a "retraction bulb." Modified from
Keller-Peck et al. (2001).
65
Spatial patterning of connectivity by synapse
elimination in the visual cortex
Axonal projections from each eye are organized
into separate eye-specific layers in the dorsal
lateral geniculate nucleus (dLGN). The axonal
terminals of dLGN neurons in each eye-specific
layer terminate and occupy adjacent territories
in layer IV, forming ocular dominance columns in
the primary visual cortex. Organized pathways
representing the left and right eyes are
separated spatially and functionally from the
retina to layer IV emerge during development from
less precise patterns of connectivity. Both dLGN
neurons and layer IV cells initially receive
converging eye input. Inputs segregate first in
the dLGN and then in the cortex.
66
The development of ocular dominance columns
LeVay S, Stryker MP, Shatz CJ, 1978
At 2 weeks, there is a continuous band of
synaptic connections in layer IV that represent
the input to the visual cortex from
geniculocortical afferents. At 6 weeks,
fluctuations in the intensity are already
apparent. By 13 weeks, the pattern of cortical
striping is similar to that seen in the adult.
The segregation of synaptic inputs within the
cortical layer depends on synaptic activity from
postnatal visual experiences.
67
Critical period for imprinting in ducklings
occurs during a few hours of the first day of
life. Ducklings were exposed once, for 10 min, to
one of several models of a male duck. Imprinting
was assessed 5 to 70 h later by offering the
ducklings a choice between the previously
presented model and a model of a female duck and
noting which of the models the ducklings
followed. (B) The plot indicates the percentage
of ducklings that scored perfectly in the
assessment of their following responses to the
imprinting model. From Ramsay and Hess (1954).
68
Effect of chronic closure of one eye on the
responsiveness of visual cortical neurons to
input from each eye.
A) Ocular dominance distribution in V1 of 3 to 4
week old kittens. Cells in group 1 are driven
only by the contralateral eye group 2,
contralateral eye is markedly dominant group 3,
contralateral eye is slightly dominant group 4,
no apparent difference in the drive from two
eyes group 5, ipsilateral eye dominates
slightly group 6, dominated markedly group 7,
cells are driven only by ipsilateral eye. B)
Ocular dominance distribution was altered
dramatically in a kitten exposed to contralateral
eye closure for 1 week from 23 to 29 days of age.
C) Ocular dominance distribution was essentially
normal in an adult cat exposed to contralateral
eye closure for 26 months. From Hubel and Wiesel
(1970).
69
R. Balice-Gordon