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Control cis-regulador del desarrollo y evolución del sistema corticoespinal
Sungbo Shim1, Kenneth Y Kwan, Mingfeng Li
1Department of Neurobiology and Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Nature
|June 9, 2012
Resumen
Los investigadores descubrieron un elemento regulador genético que controla el desarrollo de las neuronas corticospinales. Este elemento, E4, interactúa con los factores de transcripción SOX para garantizar el correcto cableado cerebral y la formación de la capa cortical en los mamíferos.
Área de la Ciencia:
- La neurociencia es la neurociencia.
- Biología del desarrollo Biología del desarrollo.
- Biología evolutiva Biología evolutiva.
Sus antecedentes:
- El neocórtex cerebral de seis capas de los mamíferos y el tracto corticospinal son innovaciones evolutivas clave.
- Los mecanismos genéticos que gobiernan el desarrollo y la evolución neocorticales no se comprenden completamente.
Objetivo del estudio:
- Identificar los elementos genéticos que regulan el desarrollo de las neuronas corticospinales.
- Para aclarar los orígenes evolutivos de las redes reguladoras del neocórtex de los mamíferos.
Principales métodos:
- Identificación de un elemento no exónico conservado (E4) que funciona como un potenciador específico de la corteza para el gen Fezf2.
- Análisis de las interacciones de SOX4, SOX11 y SOX5 con el elemento E4.
- Eliminación mediada por CRISPR de Sox4 y Sox11 en la corteza para evaluar los efectos sobre la expresión de Fezf2 y el desarrollo neuronal.
- Análisis comparativo de los sitios de unión de SOX en E4 a través de la evolución de los tetrápodos.
Principales resultados:
- E4 actúa como un potenciador crítico para Fezf2, un gen esencial para la identidad de la neurona corticospinal.
- SOX4 y SOX11 activan E4, compitiendo con el represivo SOX5.5.
- La eliminación de Sox4 y Sox11 interrumpe la expresión de Fezf2, deteriora la especificación de las neuronas corticospinales y causa defectos de laminación cortical similares a los de los carretes.
- La evidencia sugiere la evolución de sitios funcionales de unión de SOX en E4 durante la evolución de los tetrápodos y los mamíferos.
Conclusiones:
- Los factores de transcripción SOX convergen en el potenciador Fezf2 E4 para regular el desarrollo de las neuronas corticospinales.
- Esta red reguladora es crucial para establecer la identidad neuronal, la conectividad y la arquitectura cortical.
- Los hallazgos proporcionan información sobre la base genética de la evolución neocortical de los mamíferos.
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