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Rere controla la señalización del ácido retinoico y una cierta simetría bilateral
Gonçalo C Vilhais-Neto1, Mitsuji Maruhashi, Karen T Smith
1Stowers Institute for Medical Research, Missouri 64110, USA.
Nature
|February 19, 2010
Resumen
Una mutación en Rere interrumpe la simetría somática en los embriones de ratón al afectar la señalización del ácido retinoico. Este hallazgo puede explicar los defectos de la columna vertebral como la escoliosis en humanos.
Área de la Ciencia:
- Biología del desarrollo Biología del desarrollo.
- Genética La genética.
- Biología Molecular Biología Molecular
Sus antecedentes:
- La organización del plano corporal de los vertebrados se caracteriza por la simetría bilateral.
- La formación de somitas es crucial para el desarrollo esquelético y requiere una simetría precisa.
- Investigaciones anteriores indicaron un papel para el ácido retinoico en el mantenimiento de la simetría somítica.
Objetivo del estudio:
- Investigar el papel del gen Rere en el establecimiento de la simetría somática durante el desarrollo embrionario.
- Aclarar los mecanismos moleculares por los cuales Rere influye en la señalización del ácido retinoico y el patrón izquierda-derecha.
- Explorar el vínculo potencial entre la desregulación de Rere y las deformidades de la columna vertebral humana.
Principales métodos:
- Análisis de embriones de ratón con mutaciones en el gen Rere.
- Investigación de las vías de señalización del ácido retinoico e interacciones con Fgf8.8.
- Ensayos bioquímicos para caracterizar el complejo receptor del ácido Rere-Nr2f2-p300-retinoico.
- Experimentos de knockdown genético para evaluar el impacto en la expresión génica objetivo del ácido retinoico.
Principales resultados:
- Las mutaciones raras conducen a la formación de somitas asimétricas en embriones de ratón.
- Rere regula la señalización del ácido retinoico, que es esencial para mantener la simetría somítica.
- Rere interactúa con Nr2f2 y p300 para formar un complejo que promueve la transcripción del gen diana del ácido retinoico.
- La expresión asimétrica de Nr2f2 se correlaciona con una señalización alterada del ácido retinoico y una asimetría somítica.
Conclusiones:
- El gen Rere juega un papel crítico en el control de la simetría somítica a través de su regulación de la señalización del ácido retinoico.
- El complejo Rere-contenido identificado es esencial para la activación transcripcional de las dianas del ácido retinoico.
- La desregulación de este mecanismo de desarrollo puede contribuir a anomalías congénitas de la columna vertebral, incluida la escoliosis.
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