Genesis and Migration I
Associated Reading: Chapter 3
Genesis and Migration I
• Development of the nervous system requires:
• Proliferation and differentiation of progenitor neurons and glia.
• Migration of neurons and glia
• Histogenesis- differentiation into specialized tissues and groups (e.g. cerebral
cortex, basal ganglia)
Neurogenesis begins in the neural tube
Neurogenesis begins in the neural tube
Clonal analysis of progenitor cells
• Earlier cells give
rise to more clones
• Glia and neurons
can arise from the
same progenitor
cell
• Ex: In cortex,
approximately 5
neurons and 30
glia from each
progenitor
General Principles of Neurogenesis
• Length of cell cycle increases
progressively during embryogenesis
• Rat cortical progenitor cells:
• 11 hrs at E12;
• 19 hrs at E19.
• Increase in cell cycle period is largely due
to lengthening of G1
• Possibly reflects regulation of entry into S
phase
Numbers of cells generated by progenitors
depends on stage and region of development
• Early progenitor cells give rise to many more progeny than later cells.
• Cells in large regions of brain give rise to more cells.
• At early time-points, many more cells undergo symmetric division
Neurons are terminally differential
Clonal analysis of progenitor cells
• Earlier cells give
rise to more clones
• Glia and neurons
can arise from the
same progenitor
cell
• Ex: In cortex,
approximately 5
neurons and 30
glia from each
progenitor
3H-Thymidine
labeling provides information on the
cell cycle length
3H-Thymidine
Birthdating
• Pyramidal cells develop early, granule cells
develop late
• Cortex develops in an inside-out manner
• Phylogenetically older areas develop before
newer areas.
Cyclins control neuronal proliferation
How do cells become differentiated into
Neurons and Glia?
• Growth Factors
•
•
•
•
Radial Glia: GGF
Neurons: NT3, FGF2
Oligodendrocytes: PDGF, NT3, IGF-1
Astrocytes: EGF, CNTF,
• BMP2, BMP4; CTNF and BMP2 activate GFAP.
Sonic hedgehog promotes proliferation of
neurons
Notch Pathway and Neurogenesis
Summary
• Neurogenesis begins in the neural tube.
• Position in neural tube correlates with step in cell cycle.
• Length of cycle increases during embryogenesis.
• Thymidine birthdating is used to determine the length of the cell cycle and
the time of origin of cells in the nervous system.
• Cells labeled at mitosis
• Cells leaving the cell cycle will have more thymidine than those that continue to
divide.
• Ontogeny recapitulates phylogeny.
• Cortical Neurogenesis occurs late in development.
• Growth factors promote differentiation into neurons or glia.
• Sonic hedgehog promotes granule cell formation in cerebellum.