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Papel esencial de los glicosaminoglicanos en la señalización de Fgf durante la gastrulación del ratón

María J García-García¹, Kathryn V Anderson

¹Developmental Biology Program, Sloan-Kettering Institute, 1275 York Avenue, New York, NY 10021, USA.

|September 25, 2003

Resumen

Los proteoglicanos, esenciales para la comunicación celular, son cruciales para la señalización del factor de crecimiento de los fibroblastos (Fgf) durante el desarrollo embrionario. La interrupción genética de la síntesis de proteoglicanos en ratones bloquea la señalización de Fgf, lo que afecta la migración del mesodermo y el endodermo durante la gastrulación.

Área de la Ciencia:

Biología del desarrollo Biología del desarrollo.
Biología Molecular Biología Molecular
Genética La genética.

Sus antecedentes:

Los estudios in vitro sugieren que los proteoglicanos median la señalización del factor de crecimiento de los mamíferos.
La evidencia genética para este papel ha sido limitada.
Los proteoglicanos son macromoléculas complejas con cadenas de glucosaminoglicanos (GAG).

Objetivo del estudio:

Investigar el papel in vivo de los proteoglicanos en el desarrollo embrionario de mamíferos.
Para caracterizar la base genética y las consecuencias del desarrollo de la síntesis alterada de proteoglicanos.
Determinar las vías de señalización específicas del factor de crecimiento afectadas por la deficiencia de proteoglicanos.

Principales métodos:

Caracterización de una mutación de ratón inducida por la ENU, el mesodermo perezoso (lzme).
Análisis genético del gen UDP-glucosa deshidrogenasa (Ugdh), esencial para la síntesis de GAG.
Análisis fenotípico de embriones mutantes durante la gastrulación.
Análisis de marcadores moleculares para evaluar las vías de señalización del factor de crecimiento de los fibroblastos (Fgf), nodal y Wnt3.

Principales resultados:

La mutación de lzme interrumpe la UDP-glucosa deshidrogenasa (Ugdh), lo que perjudica la síntesis de proteoglicanos.
Los embriones mutantes de lzme exhiben defectos de gastrulación y migración alterada del mesodermo/endodermo.
La señalización del factor de crecimiento de los fibroblastos (Fgf) está específicamente bloqueada en embriones mutantes.
Las vías de señalización nodal y Wnt3 permanecen funcionales en los mutantes de lzme.

Conclusiones:

Se ha demostrado genéticamente que los proteoglicanos son esenciales para la señalización del factor de crecimiento de los fibroblastos (Fgf) durante la gastrulación del ratón.
Este estudio proporciona evidencia genética in vivo para el papel de los proteoglicanos en la mediación de la señalización de Fgf.
El deterioro de la síntesis de proteoglicanos conduce a defectos en el desarrollo al interrumpir específicamente los procesos dependientes de Fgf.

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