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El surgimiento de la identidad transcripcional en las neuronas somatosensoriales
Nikhil Sharma1,2, Kali Flaherty1,2, Karina Lezgiyeva1,2
1Department of Neurobiology, Harvard Medical School, Boston, MA, USA.
Nature
|January 10, 2020
Resumen
Las neuronas somatosensoriales en desarrollo comienzan sin especializarse. Las señales derivadas del objetivo guían su diversificación en subtipos distintos mediante la regulación de la expresión del factor de transcripción durante el desarrollo.
Área de la Ciencia:
- La neurociencia
- Biología del desarrollo
- La genética
Sus antecedentes:
- Las neuronas somatosensoriales primarias poseen más de doce subtipos distintos, cada uno con funciones únicas.
- Los mecanismos de desarrollo que establecen programas especializados de expresión génica en estos subtipos de neuronas siguen siendo en gran medida desconocidos.
Objetivo del estudio:
- Investigar la trayectoria de desarrollo de la maduración transcripcional en subtipos de neuronas somatosensoriales primarias.
- Para aclarar cómo los programas de expresión génica impulsan la diversificación neuronal.
Principales métodos:
- Generación de un atlas transcriptómico del linaje neuronal somatosensorial primario del ratón durante el desarrollo.
- Análisis transcriptómico de neuronas sensoriales de ratones mutantes que carecen de factores de transcripción específicos.
- Investigación de los efectos de la interrupción del factor de crecimiento nervioso (NGF) en los patrones de los factores de transcripción.
Principales resultados:
- La neurogénesis somatosensorial produce inicialmente neuronas no especializadas en la transcripción con una amplia coexpresión del factor de transcripción.
- El desarrollo implica la restricción de los factores de transcripción a subtipos neuronales específicos, coordinando la expresión génica específica del subtipo.
- La interrupción de la señalización del NGF conduce a patrones anormales de expresión del factor de transcripción, lo que indica una influencia derivada del objetivo.
Conclusiones:
- La diversificación neuronal es impulsada por un proceso de desarrollo que hace que las células pasen de un estado no especializado a uno especializado.
- Las señales derivadas del objetivo juegan un papel crucial en la diversificación neuronal al modular la selección del factor de transcripción.
- Se propone un modelo en el que las señales de campo objetivo promueven la especificación del subtipo a través de la regulación del factor de transcripción.
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