Transcript Development

Developmental Neuroscience
Halo response of
an embryonic
chick ganglion
after incubation
with nerve growth
factor. (Courtesy
of Rita LeviMontalcini)
Embryonic and Fetal Development of
the Human Brain
Actual Size
Actual Size
Photographs of Human
Fetal Brain Development
Lateral view of the human
brain shown at one-third size
at several stages of fetal
development. Note the
gradual emergence of gyri
and sulci.
Nervous System Development in the
Human Embryo
(a) At 18 days after
conception the embryo
begins to implant in the
uterine wall. It consists of
3 layers of cells:
endoderm, mesoderm,
and ectoderm. Thickening
of the ectoderm leads to
the development of the
neural plate (inserts). (b)
The neural groove begins
to develop at 20 days.
Nervous System Development in the
Human Embryo
(c) At 22 days the
neural groove closes
along the length of the
embryo making a tube.
(d) A few days later 4
major divisions of the
brain are observable –
the telencephalon,
diencephalon,
mesencephalon, and
rhombencephalon.
Eight Phases in Embryonic and Fetal
Development at a Cellular Level
1. Mitosis/Proliferation
2. Migration
3. Differentiation
4. Aggregation
5. Synaptogenesis
6. Neuron Death
7. Synapse Rearrangement
8. Myelination
8 stages are sequential
for a given neuron, but
all are occurring
simultaneously
throughout fetal
development
Eight Phases in Embryonic and Fetal
Development at a Cellular Level
1. Mitosis
2. Migration
5. Synaptogenesis 6. Death
3. Aggregation and
4. Differentiation
7. Rearrangement
8. Myelination
1. Mitosis/Proliferation
•Occurs in ventricular zone
•Rate can be 250,000/min
•After mitosis “daughter”
cells become fixed post
mitotic
1. Mitosis/Proliferation:
Neurons and Glia
At early stages, a stem cell
generates neuroblasts. Later, it
undergoes a specific asymmetric
division (the “switch point”) at
which it changes from making
neurons to making glia
2. Migration
Note that
differentiation is
going on as neurons
migrate.
2. Migration
Radial Glia
Radial glial cells
act as guide
wires for the
migration of
neurons
Growth cones crawl forward as they
elaborate the axons training behind them.
Their extension is controlled by cues in
their outside environment that ultimately
direct them toward their appropriate
targets.
2. Migration
Growth Cones
The fine threadlike
extensions shown in red
and green are filopodia,
which find adhesive
surfaces and pull the
growth cone and
therefore the growing
axon to the right.
2. Migration
Growth Cones
Scanning electron micrograph of a growth cone
in culture. On a flat surface growth cones are
very thin. They have numerous filopodia
Ramon y Cajal drew these
growth cones showing their
variable morphology
2. Migration: How Do Neurons
“Know” Where to Go?
There are extrinsic and intrinsic
determinants of neurons’ fate.
A. Extrinsic signals
B. Different sources of extrinsic
signals
C. Generic signal transduction
pathway
D. Intrinsic determinants
3. Differentiation
•Neurons become fixed
post mitotic and
specialized
•They develop processes
(axons and dendrites)
•They develop NTmaking ability
•They develop electrical
conduction
3. Differentiation
Development of the cerebral cortex
The ventricular zone (VZ) contains progenitors of neurons and glia. 1st neurons establish
the preplate (PP); their axons an ingrowing axons from the thalamus establish the
intermediate zone (IZ). Later generated neurons establish layers II-VI. After migration
and differentiation there are 6 cortical layers.
4. Aggregation
Like neurons move
together and form
layers
5. Synaptogenesis
Axons (with
growth cones on
end) form a
synapse with other
neurons or tissue
(e.g. muscle)
5. Synaptogenesis: Attraction to Target
Cells
Target cells release a chemical that
creates a gradient (dots) around them.
Growth cones orient to and follow the
gradient to the cells. The extensions
visible in c are growing out of a sensory
ganglion (left) toward their normal target
tissue. The chemorepellent protein Slit
(red) in an embryo of the fruit fly repels
most axons.
6. Neuron Death
•Between 40 and 75
percent of all neurons born
in embryonic and fetal
development do not
survive.
•They fail to make optimal
synapses.
Neuron Death Leads to Synapse
Rearrangement
Release and uptake
of neurotrophic
factors
Neurons receiving
Axonal processes
insufficient neurotropic complete for limited
factor die
neurotrophic factor
7. Synapse Rearrangement
•Active synapses
likely take up
neurotrophic factor
that maintains the
synapse
•Inactive synapses
get too little trophic
factor to remain
stable
7. Synapse Rearrangement
Time-lapse imaging of synapse elimination
Two neuromuscular
junctions (NM1 and
NMJ2) were viewed in
vivo on postnatal days 7,
8, and 9.
8. Myelination
Myelination Lasts for up to 30 Years
Brain Weight During Development
and Aging
Critical Periods
Teratogens
Greek – “teratos” – wonder or monster
“genos” - birth
1. Physical agents (e.g., x-rays)
2. Chemicals (e.g., drugs)
3. Microorganisms (e.g., rubella)