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El control molecular de las fuerzas macroscópicas impulsa la formación del intestino trasero de los vertebrados
Nandan L Nerurkar1,2,3, ChangHee Lee4, L Mahadevan5,6,7,8
1Department of Genetics, Harvard Medical School, Boston, MA, USA. nln2113@columbia.edu.
Nature
|January 18, 2019
Resumen
La formación temprana del tubo intestinal embrionario, particularmente el desarrollo del intestino posterior, es impulsada por movimientos celulares colectivos y un gradiente de fuerza contráctil. Este gradiente, influenciado por la señalización del factor de crecimiento de los fibroblastos, guía el alargamiento del tejido y el reclutamiento celular para una organogénesis adecuada.
Área de la Ciencia:
- Biología del desarrollo
- Biología celular
- La biofísica
Sus antecedentes:
- El tubo intestinal embrionario forma la base de las vías respiratorias y gastrointestinales.
- El desarrollo temprano del endodermo y la organogénesis posterior se estudian, pero la formación del tubo intestinal se entiende menos.
- Los modelos existentes describen la formación del tubo intestinal a través de portales migratorios (AIP y CIP), especialmente para el intestino anterior.
Objetivo del estudio:
- Investigar el control molecular de las fuerzas en la morfogénesis temprana del tubo intestinal embrionario.
- Aclarar el mecanismo distinto de la formación del intestino posterior.
- Identificar las vías de señalización y las fuerzas físicas que impulsan el desarrollo del intestino posterior.
Principales métodos:
- Imágenes in vivo de embriones de pollo.
- Análisis biofísico y modelado matemático.
- Las técnicas moleculares y embriológicas.
Principales resultados:
- El hindgut se forma a través de movimientos celulares colectivos, no de migración CIP.
- Un gradiente de fuerza contráctil impulsa la extensión posterior del intestino posterior.
- El gradiente de señalización del factor de crecimiento de los fibroblastos (FGF) establece el gradiente de fuerza.
- Un bucle de retroalimentación positiva recluta células en el intestino trasero alargado.
Conclusiones:
- El desarrollo del intestino posterior implica mecanismos distintos de la formación del intestino anterior.
- Las fuerzas a escala de tejido son cruciales para la morfogénesis de los vertebrados y se pueden rastrear a las señales de desarrollo.
- La señalización FGF y la contractilidad celular interactúan para impulsar el alargamiento del tubo intestinal.
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