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
Neuronjournal_title
Neuronauthors
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 FDdoi
10.1016/s0896-6273(02)01026-7subject
Has Abstractpub_date
2002-11-14 00:00:00pages
597-610issue
4eissn
0896-6273issn
1097-4199pii
S0896627302010267journal_volume
36pub_type
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