An essential role for a MEK-C/EBP pathway during growth factor-regulated cortical neurogenesis.
Neuron
; 36(4): 597-610, 2002 Nov 14.
Article
em En
| MEDLINE
| ID: mdl-12441050
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.
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Base de dados:
MEDLINE
Assunto principal:
Células-Tronco
/
Fatores de Transcrição
/
Córtex Cerebral
/
Substâncias de Crescimento
/
Proteínas Serina-Treonina Quinases
/
Regulação da Expressão Gênica no Desenvolvimento
/
Quinases de Proteína Quinase Ativadas por Mitógeno
/
Proteínas Estimuladoras de Ligação a CCAAT
/
Neurônios
Idioma:
En
Ano de publicação:
2002
Tipo de documento:
Article