Events that remove cells Progressive restriction from the epidermal of developmental lineage potential

The ectoderm: neurulation, neural tube, neural crest

Taube P. Rothman [email protected]

Neural Shaping the neural plate induction

18 days

PRIMARY NEURULATION

Neural induction, Wnt Wnt formation of the neural plate Dorsal and Wnt Wnt ventral Formation of of the neural signaling in the groove and neural folds spinal cord

Closure of neural Neural crest folds, formation of neural tube and neural crest

Initially, the neural tube is composed of a single layer of neuroepithelial cells

1 Dorsal view: Neurulating embryos Dorsal view: Neurulating embryos REGIONS OF NEURAL TUBE CLOSURE

Days 21-22 Day 23 cranioschisis meningomyecele

REGIONALIZATION OF THE CNS PRIMARY AND SECONDARY VESICLES AND FLEXURES

Cephalic Rhombomere flexure

Cervical flexure

NEUROGENESIS IN THE NEUROEPITHELIUM How are billions of CNS cells (neurons and glia) generated?

lumen

Cerebral cortex

lumen

Post mitotic daughter cell

Lumen Nuclei (but not cells) migrate during the cell The plane of division of progenitor cells in the cycle ventricular zone influences their fate

The neuroepithelium is a single layer of rapidly dividing stem cells

2 At least half the neurons that are generated undergo apoptosis and die.

Neuronal survival depends upon recognition of target related trophic signals. Ectomesenchyme

The neural crest

Neural crest cells are guided through permissive Wnt BMP environments to RhoB reach their targets

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Ephrin proteins inhibit neural crest migration

THE REGION OF THE NEURAXIS FROM WHICH A CREST CELL MIGRATES DETERMINES THE TARGET REACHED BY ITS DERIVATIVES

cranial circumpharyngeal neural crest

truncal cardiac vagal

truncal

sacral

3 Genetic potential, developmental restriction and differentiation

•Some neural crest cells appear to be pluripotent. They can generate a remarkable number of differentiated cell types, but express only those phenotypes that are appropriate for the region they colonize. •Example: Cranial neural crest ectoderm: •The genetic potential of other crest-derived The fates of these crest derived cells cells is more restricted. There are a limited are controlled by the specific growth neurulation, neural tube, neural crest number of options in their genetic factors they encounter repertoire. The end •Example: truncal neural crest

•Finally, some pre-migratory crest cells appear to be programmed for a specific developmental fate or if they are not committed to one before leaving the crest, there developmental options are severely Taube P. Rothman restricted during their migration. [email protected] •Example: cardiac neural crest

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