Negative regulation of Yap during neuronal differentiation.
Dev Biol
; 361(1): 103-15, 2012 Jan 01.
Article
em En
| MEDLINE
| ID: mdl-22037235
ABSTRACT
Regulated proliferation and cell cycle exit are essential aspects of neurogenesis. The Yap transcriptional coactivator controls proliferation in a variety of tissues during development, and this activity is negatively regulated by kinases in the Hippo signaling pathway. We find that Yap is expressed in mitotic mouse retinal progenitors and it is downregulated during neuronal differentiation. Forced expression of Yap prolongs proliferation in the postnatal mouse retina, whereas inhibition of Yap by RNA interference (RNAi) decreases proliferation and increases differentiation. We show Yap is subject to post-translational inhibition in the retina, and also downregulated at the level of mRNA expression. Using a cell culture model, we find that expression of the proneural basic helix-loop-helix (bHLH) transcription factors Neurog2 or Ascl1 downregulates Yap mRNA levels, and simultaneously inhibits Yap protein via activation of the Lats1 and/or Lats2 kinases. Conversely, overexpression of Yap prevents proneural bHLH proteins from initiating cell cycle exit. We propose that mutual inhibition between proneural bHLH proteins and Yap is an important regulator of proliferation and cell cycle exit during mammalian neurogenesis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosfoproteínas
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Retina
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Diferenciação Celular
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Regulação da Expressão Gênica no Desenvolvimento
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Proteínas Adaptadoras de Transdução de Sinal
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Fatores de Transcrição Hélice-Alça-Hélice Básicos
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Neurogênese
/
Neurônios
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Dev Biol
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos