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 Devjournal_title
Genes & developmentauthors
Nguyen L,Besson A,Heng JI,Schuurmans C,Teboul L,Parras C,Philpott A,Roberts JM,Guillemot Fdoi
10.1101/gad.377106subject
Has Abstractpub_date
2006-06-01 00:00:00pages
1511-24issue
11eissn
0890-9369issn
1549-5477pii
gad.377106journal_volume
20pub_type
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