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Regulación transcripcional de la migración de las neuronas corticales por factores del dominio POU
Robert J McEvilly1, Marcela Ortiz de Diaz, Marcus D Schonemann
1Howard Hughes Medical Institute, Department and School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92037-0648, USA.
Science (New York, N.Y.)
|February 23, 2002
Resumen
Los factores de transcripción Brn-1 y Brn-2 regulan el desarrollo cortical controlando la migración de las neuronas. Su ausencia conduce a graves defectos en la estructura cerebral, específicamente la inversión cortical en ratones.
Área de la Ciencia:
- La neurociencia es la neurociencia.
- Biología del desarrollo Biología del desarrollo.
- Biología Molecular Biología Molecular
Sus antecedentes:
- La correcta laminación de la corteza cerebral de los mamíferos es crucial para la función cognitiva.
- Se sabe que la cinasa Cdk5 y el ligando reelin median las vías de desarrollo cortical.
- Comprender los mecanismos moleculares del desarrollo cortical es un área de investigación en curso.
Objetivo del estudio:
- Para identificar los reguladores clave de la laminación cortical mediada por Cdk5.
- Investigar los roles de los factores de transcripción del dominio POU de clase III, Brn-1 y Brn-2, en el desarrollo del cerebro anterior.
- Aclarar los mecanismos moleculares por los cuales Brn-1 y Brn-2 controlan la migración neuronal y el desarrollo cortical.
Principales métodos:
- Análisis genético de la función de Brn-1 y Brn-2 en modelos de ratón.
- Análisis de la expresión génica para las subunidades reguladoras de Cdk5 (p35 y p39).
- Examen de la laminación cortical y la migración neuronal en ratones de tipo salvaje y knockout.
Principales resultados:
- Brn-1 y Brn-2 se coexpresan en la mayoría de las neuronas corticales de la capa II-V.
- Brn-1 y Brn-2 regulan redundantemente la expresión celular autónoma de p35 y p39 en las neuronas migratorias.
- Los ratones Brn-1(-/-) /Brn-2(-/-) muestran una malformación cortical severa conocida como inversión cortical.
- Estos factores de transcripción controlan críticamente el inicio de la migración radial durante el desarrollo cortical.
Conclusiones:
- Brn-1 y Brn-2 son reguladores esenciales de la laminación cortical mediada por Cdk5.
- Estos factores juegan un papel crítico y redundante en el inicio de la migración radial de las neuronas corticales.
- La interrupción de la función de Brn-1 y Brn-2 conduce a defectos profundos en el desarrollo de la corteza cerebral.
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