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El cruce de señalización secuencial regula la segregación del endomesodermo en los embriones de erizo de mar
Aditya J Sethi1, Radhika M Wikramanayake, Robert C Angerer
1National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
Science (New York, N.Y.)
|February 4, 2012
Resumen
La señalización notch y la señalización Wnt trabajan juntas para separar el endomesodermo embrionario en endodermo y mesodermo. Este proceso implica que Notch inhiba los genes endodermales en el mesodermo y Wnt refuerza el destino endodermal.
Área de la Ciencia:
- Biología del desarrollo Biología del desarrollo.
- La señalización celular de las células.
- Genética La genética.
Sus antecedentes:
- Los mecanismos precisos que rigen la segregación del endomesodermo embrionario en linajes distintos de endodermo y mesodermo en los deuterostomas aún no se comprenden por completo.
- Comprender este proceso de desarrollo fundamental es crucial para comprender la embriogénesis temprana y los posibles trastornos del desarrollo.
Objetivo del estudio:
- Para dilucidar las vías moleculares y las interacciones de señalización que regulan la segregación del endomesodermo en embriones deuteróstomos.
- Investigar las funciones de la señalización de Notch y Wnt en el establecimiento de destinos separados de endodermo y mesodermo.
Principales métodos:
- Utilizó embriones de erizo de mar como un sistema modelo para estudiar el desarrollo embrionario temprano.
- Empleó técnicas de biología molecular para analizar patrones de expresión génica y localización de proteínas.
- Investigó la interacción entre la señalización Notch y las vías de señalización Wnt durante la diferenciación del endomesodermo.
Principales resultados:
- Se demostró que la señalización de Notch inicia la segregación del endomesodermo mediante la supresión de un factor de transcripción clave del endodermo en el mesodermo presunto.
- Se identificó un circuito regulador donde el factor de transcripción endodérmica mantiene la expresión canónica del ligando Wnt (cWnt) específicamente en los precursores endodérmicos.
- Se demostró que la exportación nuclear dependiente de Notch de un coactivador transcripcional de la β-catenina en el mesodermo lo hace no responder a las señales cWnt, aislándolo así de un destino endodermal.
Conclusiones:
- La segregación del endomesodermo es un proceso progresivo de varios pasos orquestado por interacciones secuenciales entre las vías de señalización Notch y Wnt.
- Este estudio revela un nuevo mecanismo regulador que controla las decisiones del destino celular durante el desarrollo temprano del deuteroestoma.
- Los hallazgos proporcionan información crítica sobre la base molecular de la especificación de la capa germinal.
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