p27kip1 independently promotes neuronal differentiation and migration in the cerebral cortex.

Abstract:

:The generation of neurons by progenitor cells involves the tight coordination of multiple cellular activities, including cell cycle exit, initiation of neuronal differentiation, and cell migration. The mechanisms that integrate these different events into a coherent developmental program are not well understood. Here we show that the cyclin-dependent kinase inhibitor p27(Kip1) plays an important role in neurogenesis in the mouse cerebral cortex by promoting the differentiation and radial migration of cortical projection neurons. Importantly, these two functions of p27(Kip1) involve distinct activities, which are independent of its role in cell cycle regulation. p27(Kip1) promotes neuronal differentiation by stabilizing Neurogenin2 protein, an activity carried by the N-terminal half of the protein. p27(Kip1) promotes neuronal migration by blocking RhoA signaling, an activity that resides in its C-terminal half. Thus, p27(Kip1) plays a key role in cortical development, acting as a modular protein that independently regulates and couples multiple cellular pathways contributing to neurogenesis.

journal_name

Genes Dev

journal_title

Genes & development

authors

Nguyen L,Besson A,Heng JI,Schuurmans C,Teboul L,Parras C,Philpott A,Roberts JM,Guillemot F

doi

10.1101/gad.377106

subject

Has Abstract

pub_date

2006-06-01 00:00:00

pages

1511-24

issue

11

eissn

0890-9369

issn

1549-5477

pii

gad.377106

journal_volume

20

pub_type

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