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La evolución de la regulación génica en el desarrollo del cerebelo de mamíferos

Ioannis Sarropoulos¹, Mari Sepp¹, Tetsuya Yamada¹

¹Center for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH Alliance, Heidelberg, Germany.

Science (New York, N.Y.)

|January 29, 2026

Resumen

Se exploraron las redes reguladoras de genes que impulsan la evolución del cerebelo utilizando datos de un solo núcleo de seis mamíferos. Esto reveló códigos conservados y programas específicos del linaje, incluidos cambios recientes en las células progenitoras cerebelares humanas.

Área de la Ciencia:

Biología evolutiva Biología evolutiva.
La neurociencia es la neurociencia.
La genómica es la genómica.

Sus antecedentes:

Los cambios reguladores genéticos son clave para las innovaciones evolutivas, como el cerebelo humano expandido.
Comprender estos cambios en el desarrollo del cerebelo es crucial, pero en gran medida inexplorado.

Objetivo del estudio:

Investigar las redes de regulación genética conservadas y divergentes en el desarrollo del cerebelo en los mamíferos.
Identificar los elementos reguladores y los cambios genéticos asociados con la evolución humana.

Principales métodos:

Mediciones de la expresión génica de un solo núcleo y la accesibilidad a la cromatina de seis especies de mamíferos (humano, bonobo, macaco, marmota, ratón, zarigüey).
Desarrollo de modelos basados en secuencias para predecir códigos regulatorios.
Predicción de la accesibilidad de la cromatina en 240 especies de mamíferos para reconstruir las historias evolutivas.

Principales resultados:

Identificación de los reguladores centrales de la identidad de las células cerebelares y códigos reguladores conservados.
Reconstrucción de las historias evolutivas para los elementos cis-reguladores humanos.
Descubrimiento de elementos cis-reguladores bajo selección positiva y asociados con cambios en la expresión génica, incluida la ganancia de expresión THRB en células progenitoras cerebelares humanas.

Conclusiones:

Los programas de regulación genética que gobiernan el desarrollo del cerebelo son compartidos entre los mamíferos y específicos de ciertos linajes.
Este estudio proporciona información sobre los fundamentos regulatorios de la evolución del cerebelo y los rasgos específicos del ser humano.

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