Selective induction of neocortical GABAergic neurons by the PDK1-Akt pathway through activation of Mash1.
Proc Natl Acad Sci U S A
; 106(31): 13064-9, 2009 Aug 04.
Article
en En
| MEDLINE
| ID: mdl-19549840
ABSTRACT
Extracellular stimuli regulate neuronal differentiation and subtype specification during brain development, although the intracellular signaling pathways that mediate these processes remain largely unclear. We now show that the PDK1-Akt pathway regulates differentiation of telencephalic neural precursor cells (NPCs). Active Akt promotes differentiation of NPC into gamma-aminobutyric acid-containing (GABAergic) but not glutamatergic neurons. Disruption of the Pdk1 gene or expression of dominant-negative forms of Akt suppresses insulin-like growth factor (IGF)-1 enhancement of NPC differentiation into neurons in vitro and production of neocortical GABAergic neurons in vivo. Furthermore, active Akt increased the protein levels and transactivation activity of Mash1, a proneural basic helix-loop-helix protein required for the generation of neocortical GABAergic neurons, and Mash1 was required for Akt-induced neuronal differentiation. These results have unveiled an unexpected role of the PDK1-Akt pathway a key mediator of extracellular signals regulating the production of neocortical GABAergic neurons.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Células Madre
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Transducción de Señal
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Diferenciación Celular
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Proteínas Serina-Treonina Quinasas
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Neocórtex
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Proteínas Proto-Oncogénicas c-akt
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Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico
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Ácido gamma-Aminobutírico
Límite:
Animals
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2009
Tipo del documento:
Article
País de afiliación:
Japón