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Real-time Bioluminescence Imaging of Notch Signaling Dynamics during Murine Neurogenesis
Published on: December 12, 2019
La interacción entre Notch y la vía EGFR regula el número de células madre neurales y la autorrenovación
Adan Aguirre1, Maria E Rubio, Vittorio Gallo
1Center for Neuroscience Research, Children's National Medical Center, Washington, District of Columbia 20010, USA.
Nature
|September 17, 2010
Resumen
El equilibrio de las células madre neurales (CNS) y las células progenitoras neurales (NPC) en el cerebro adulto.
Área de la Ciencia:
- La neurociencia es la neurociencia.
- Biología de las células madre Biología de las células madre
- La señalización celular de las células.
Sus antecedentes:
- Los microambientes celulares, o nichos, regulan el comportamiento de las células madre, incluida la autorrenovación y el destino.
- La zona subventricular (SVZ) del cerebro adulto alberga células madre neurales (NSC) y células progenitoras neurales (NPC).
- El mantenimiento del equilibrio entre las NSC y las NPC en la SVZ es crucial para la función cerebral y la reparación.
Objetivo del estudio:
- Investigar la interacción entre el receptor del factor de crecimiento epidérmico (EGFR) y las vías de señalización de Notch en el mantenimiento de las poblaciones de NSC y NPC dentro del nicho SVZ.
- Aclarar el mecanismo por el cual las interacciones de señalización de EGFR y Notch regulan el equilibrio de las células madre neurales y las células progenitoras en el cerebro adulto.
Principales métodos:
- Estudios in vivo que utilizan el modelo de nicho de SVZ para adultos.
- Manipulación de la señalización del EGFR para evaluar su impacto en las poblaciones de NSC y NPC.
- Análisis de las interacciones célula-célula y el cruce de vías de señalización (EGFR y Notch).
Principales resultados:
- La mejora de la señalización del EGFR in vivo conduce a una expansión del grupo de NPC.
- El aumento de la señalización del EGFR reduce el número de NSC y dificulta la auto-renovación de las NSC.
- Este efecto está mediado por un mecanismo no celular autónomo donde la señalización EGFR regula la señalización Notch.
Conclusiones:
- Se identifica una nueva interacción entre las vías de señalización de EGFR y Notch en el SVZ adulto.
- Este cruce es crítico para mantener el equilibrio entre las células madre neurales y las células progenitoras.
- Los hallazgos proporcionan un mecanismo clave para regular el mantenimiento de la piscina de NSC y NPC en el cerebro adulto.
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The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
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