Journal
CEREBRAL CORTEX
Volume 15, Issue 9, Pages 1343-1355Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/cercor/bhi017
Keywords
cell cycle; cell specification; neurogenesis; p27(Kip1); tet-system
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Funding
- NINDS NIH HHS [R01 NS012005, NS12005, R01 NS043426, NS43246] Funding Source: Medline
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Neocortical projection neurons arise from a pseudostratified ventricular epithelium (PVE) from embryonic day 11 (E11) to E17 in mice. The sequence of neuron origin is systematically related to mechanisms that specify neuronal class properties including laminar fate destination. Thus, the neurons to be assembled into the deeper layers are the earliest generated, while those to be assembled into superficial layers are the later generated neurons. The sequence of neuron origin also correlates with the probability of cell cycle exit ((I) and the duration of G1-phase of the cell cycle (T-G1) in the PVE. Both Q and T-G1 increase as neuronogenesis proceeds. We test the hypothesis that mechanisms regulating specification of neuronal laminar destination, (I and T-G1 are coordinately regulated. We find that overexpression of p27(Kip1) in the PVE from E12 to E14 increases (I but not TG1 and that the increased (I is associated with a commensurate increase in the proportion of exiting cells that is directed to superficial layers. We conclude that mechanisms that govern specification of neocortical neuronal laminar destination are coordinately regulated with mechanisms that regulate (I and are independent of mechanisms regulatory to cell cycle duration. Moreover, they operate prior to postproliferative mechanisms necessary to neocortical laminar assembly.
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