Gli3 controls the onset of cortical neurogenesis by regulating the radial glial cell cycle through Cdk6 expression.
Development
; 145(17)2018 08 20.
Article
en En
| MEDLINE
| ID: mdl-30093555
ABSTRACT
The cerebral cortex contains an enormous number of neurons, allowing it to perform highly complex neural tasks. Understanding how these neurons develop at the correct time and place and in accurate numbers constitutes a major challenge. Here, we demonstrate a novel role for Gli3, a key regulator of cortical development, in cortical neurogenesis. We show that the onset of neuron formation is delayed in Gli3 conditional mouse mutants. Gene expression profiling and cell cycle measurements indicate that shortening of the G1 and S phases in radial glial cells precedes this delay. Reduced G1 length correlates with an upregulation of the cyclin-dependent kinase gene Cdk6, which is directly regulated by Gli3. Moreover, pharmacological interference with Cdk6 function rescues the delayed neurogenesis in Gli3 mutant embryos. Overall, our data indicate that Gli3 controls the onset of cortical neurogenesis by determining the levels of Cdk6 expression, thereby regulating neuronal output and cortical size.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Regulación Enzimológica de la Expresión Génica
/
Ciclo Celular
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Corteza Cerebral
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Neuroglía
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Regulación del Desarrollo de la Expresión Génica
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Quinasa 6 Dependiente de la Ciclina
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Neurogénesis
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Proteína Gli3 con Dedos de Zinc
/
Proteínas del Tejido Nervioso
Límite:
Animals
Idioma:
En
Revista:
Development
Asunto de la revista:
BIOLOGIA
/
EMBRIOLOGIA
Año:
2018
Tipo del documento:
Article
País de afiliación:
Reino Unido