5-350 Lecture Notes - Lecture 10: Axon Guidance, Cyclic Adenosine Monophosphate, Cadherin

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Outline of Lecture 10
Central Nervous System: Development and Molecular Mechanisms
I. Regionalization of neural epithelium
A) From neural plate to neural tube
- Rehash of previous lectures (neural plate, retinoic acid, Hox, Shh, notochord,
floor plate, neural tube)
- Neural tube defects (e.g. spina bifida) associated with folic acid
deficiency
B) Regional structure of neural tube
- A to P structures: telencephalon (ant. forebrain), diencephalons (post. forebrain),
mesencephalon (midbrain), rhombencephalon (hindbrain), spinal cord (see
fates on p. 3)
- D to V structures: alar plate (dorsal, sensory info) and basal plate (ventral,
motor/hormonal control nerves)
- These features combine: spinal cord and brain have alar and basal
divisions
II. Growth and differentiation
A) Neural epithelium
- Neural tube is a single layer of epithelium; lumen = ventricular, outer =
pial
- Neural precursor cell’s nucleus moves up and down during cell cycle; division
gives rise to neurons and glial cells
- Cerebral cortex develops by waves of cells that migrate from ventricular
to pial surface
- Lissencephaly develops if LIS1 or DCX genes involved in migration are
mutated
- Some cells migrate anteriorly, e.g. olfactory neurons (and continue in
adult)
B) Neurons and glial cells
- Classic neuron features: axon, synapse, dendrites, neurotransmitters
- 5 basic neuron cell types: purkinje, golgi, basket, granule, stellate
- Glial cells provide scaffold for neurons and may regulate their activity
- 2 basic glial cells: astrocytes (metabolic func.), oligodendrocytes
(insulation)
- Glial cells far outnumber neurons; glial cells can divide but neurons
cannot
C) Some CNS cells derive from committed precursors but most cell types arise
from postmitotic commitment
D) Role of Notch and Delta in commitment to differentiation
- Committed neural cells express surface bound ligand delta
- Delta binds to its receptor Notch on neighboring cells, signals for repression of
neurogenin, thereby inhibiting differentiation in nearby cells
E) Some neurons in forebrain arise in adult from neural stem cells
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