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

被引：179

作者：

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

机构：

[1] Univ Toronto, Inst Res, Hosp Sick Children, Toronto, ON M5G 1X8, Canada

[2] McGill Univ, Ctr Neuronal Survival, Montreal Neurol Inst, Royal Victoria Hosp, Montreal, PQ, Canada

[3] McGill Univ, Brain Tumor Res Ctr, Montreal Neurol Inst, Royal Victoria Hosp, Montreal, PQ, Canada

[4] Natl Canc Inst, Frederick, MD 21702 USA

[5] NCI, NIH, Bethesda, MD 20892 USA

来源：

NEURON | 2002年 / 36卷 / 04期

基金：

加拿大健康研究院;

关键词：

D O I：

10.1016/S0896-6273(02)01026-7

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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, 6 MEK-C/EBP pathway, that is essential for cortical progenitor cells to become post-mitotic 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 I 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.

引用

页码：597 / 610

页数：14

共 43 条

[1] Generation of truncated C/EBPβ isoforms by in vitro proteolysis [J].