FoxOs cooperatively regulate diverse pathways governing neural stem cell homeostasis.
Cell Stem Cell
; 5(5): 540-53, 2009 Nov 06.
Article
en En
| MEDLINE
| ID: mdl-19896444
ABSTRACT
The PI3K-AKT-FoxO pathway is integral to lifespan regulation in lower organisms and essential for the stability of long-lived cells in mammals. Here, we report the impact of combined FoxO1, 3, and 4 deficiencies on mammalian brain physiology with a particular emphasis on the study of the neural stem/progenitor cell (NSC) pool. We show that the FoxO family plays a prominent role in NSC proliferation and renewal. FoxO-deficient mice show initial increased brain size and proliferation of neural progenitor cells during early postnatal life, followed by precocious significant decline in the NSC pool and accompanying neurogenesis in adult brains. Mechanistically, integrated transcriptomic, promoter, and functional analyses of FoxO-deficient NSC cultures identified direct gene targets with known links to the regulation of human brain size and the control of cellular proliferation, differentiation, and oxidative defense. Thus, the FoxO family coordinately regulates diverse genes and pathways to govern key aspects of NSC homeostasis in the mammalian brain.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Encéfalo
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Regulación del Desarrollo de la Expresión Génica
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Células Madre Multipotentes
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Factores de Transcripción Forkhead
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Proteínas del Tejido Nervioso
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Cell Stem Cell
Año:
2009
Tipo del documento:
Article