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Interacción entre las moléculas de señalización WNT7a y SHH durante el desarrollo de las extremidades de los
1Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Cell
|March 24, 1995
Resumen
La señalización ectodérmica dorsal y Wnt7a son cruciales para mantener la expresión del Sonic hedgehog (SHH), esencial para el desarrollo de las extremidades de los vertebrados y el patrón esquelético posterior. Este estudio revela un vínculo entre las señales de patrones dorsoventrales y el crecimiento excesivo de las extremidades.
Área de la Ciencia:
- Biología del desarrollo Biología del desarrollo.
- Biología Molecular Biología Molecular
- Genética La genética.
Sus antecedentes:
- El desarrollo de las extremidades de los vertebrados implica una compleja señalización entre la cresta ectodérmica apical (AER), el mesénquima posterior y la ectoderma no cresta.
- El factor de crecimiento de fibroblastos 4 (FGF4) de la AER y el erizo sónico (SHH) del mesénquima posterior son moléculas de señalización clave.
Objetivo del estudio:
- Para investigar el papel del ectodermo dorsal en el patrón de las extremidades.
- Aclarar las vías de señalización que unen el patrón dorsoventral con el crecimiento de las extremidades y el patrón anteroposterior.
Principales métodos:
- Extirpación experimental del ectodermo dorsal en miembros en desarrollo.
- Evaluación de los niveles de expresión de Sonic hedgehog (Shh).
- Análisis de la formación de elementos esqueléticos.
- Experimentos de rescate utilizando SHH exógeno.
- Investigación de la expresión y función de Wnt7a.
Principales resultados:
- Se requiere ectodermo dorsal, junto con FGF4, para mantener la expresión Shh.
- La extirpación del ectodermo dorsal conduce a la pérdida de los elementos esqueléticos posteriores.
- La SHH exógena puede rescatar la pérdida de elementos esqueléticos posteriores.
- Wnt7a, expresado en el ectodermo dorsal, proporciona la señal necesaria para la expresión de Shh y la formación de la estructura posterior.
Conclusiones:
- La señalización Wnt7a del ectodermo dorsal es esencial para mantener la expresión Shh y el patrón adecuado de las extremidades.
- Este estudio demuestra un vínculo intrincado entre el eje dorsoventral (Wnt7a) y el eje anteroposterior (SHH) durante el desarrollo de las extremidades.
- El crecimiento y el patrón de las extremidades están coordinados por la interacción de las vías de señalización WNT7a, FGF4 y SHH a través de múltiples ejes.
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