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La vía Wnt/beta-catenina regula la formación de las válvulas cardíacas
Adam F L Hurlstone1, Anna-Pavlina G Haramis, Erno Wienholds
1Netherlands Institute for Developmental Biology, Hubrecht Laboratory and Centre for Biomedical Genetics, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands.
Nature
|October 10, 2003
Resumen
La poliposis coli adenomatosa truncada (Apc) activa la señalización de Wnt/beta-catenina, causando defectos cardíacos en el pez cebra. Esta vía es crucial para la determinación del destino celular endocárdico durante el desarrollo.
Área de la Ciencia:
- Biología del desarrollo Biología del desarrollo.
- Biología Molecular Biología Molecular
- Biología Cardiovascular Biología Cardiovascular
Sus antecedentes:
- La poliposis coli adenomatosa truncada (Apc) constitutivamente activa la vía de señalización Wnt/beta-catenina.
- El Apc juega un papel crítico en el desarrollo embrionario, ya que el Apc truncado previene la gastrulación en ratones.
Objetivo del estudio:
- Investigar el papel del Apc truncado en el desarrollo del pez cebra.
- Aclarar los efectos específicos de la señalización de Wnt/beta-catenina en el desarrollo del corazón y el destino de las células endocárdicas.
Principales métodos:
- Pez cebra generado con Apc. truncado.
- Se analizó el bucle cardíaco, la formación del cojín endocardiano y la localización de la beta-catenina.
- Utilizó los ensayos del reportero Tcf y evaluó la expresión del marcador valvular.
- Se examinó la proliferación celular y la transición epitelial-mesenquimal.
Principales resultados:
- Los peces cebra con Apc truncado completan la gastrulación, pero presentan defectos en el circuito cardíaco y una excesiva formación de almohadillas endocárdicas.
- La sobreexpresión del inhibidor de Apc o Wnt Dkk1 impidió la formación de cojines.
- Los corazones mutantes mostraron una actividad generalizada de beta-catenina nuclear y Tcf reporter, a diferencia de los corazones de tipo salvaje donde estaba restringido a las células formadoras de válvulas.
- Los marcadores de la válvula estaban regulados al alza, y la proliferación / transición epitelio-mesenquimal ocurrió en todo el endocardio.
Conclusiones:
- La señalización de Wnt/beta-catenina es esencial para el desarrollo normal del corazón en el pez cebra.
- La activación aberrante de esta vía conduce a malformaciones cardíacas al alterar el destino de las células endocárdicas.
- Se identificó un nuevo papel para la señalización de Wnt/beta-catenina en la regulación del destino de las células endocárdicas y el desarrollo de las válvulas.
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