An essential role for a MEK-C/EBP pathway during growth factor-regulated cortical neurogenesis.

Abstract:

:Mammalian neurogenesis is determined by an interplay between intrinsic genetic mechanisms and extrinsic cues such as growth factors. Here we have defined a signaling cascade, a MEK-C/EBP pathway, that is essential for cortical progenitor cells to become postmitotic neurons. Inhibition of MEK or of the C/EBP family of transcription factors inhibits neurogenesis while expression of a C/EBPbeta mutant that is a phosphorylation-mimic at a MEK-Rsk site enhances neurogenesis. C/EBP mediates this positive effect by direct transcriptional activation of neuron-specific genes such as Talpha1 alpha-tubulin. Conversely, inhibition of C/EBP-dependent transcription enhances CNTF-mediated generation of astrocytes from the same progenitor cells. Thus, activation of a MEK-C/EBP pathway enhances neurogenesis and inhibits gliogenesis, thereby providing a mechanism whereby growth factors can selectively bias progenitors to become neurons during development.

journal_name

Neuron

journal_title

Neuron

authors

Ménard C,Hein P,Paquin A,Savelson A,Yang XM,Lederfein D,Barnabé-Heider F,Mir AA,Sterneck E,Peterson AC,Johnson PF,Vinson C,Miller FD

doi

10.1016/s0896-6273(02)01026-7

subject

Has Abstract

pub_date

2002-11-14 00:00:00

pages

597-610

issue

4

eissn

0896-6273

issn

1097-4199

pii

S0896627302010267

journal_volume

36

pub_type

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