Oxidative stress regulates progenitor behavior and cortical neurogenesis.
Development
; 147(5)2020 03 11.
Article
em En
| MEDLINE
| ID: mdl-32041791
ABSTRACT
Orderly division of radial glial progenitors (RGPs) in the developing mammalian cerebral cortex generates deep and superficial layer neurons progressively. However, the mechanisms that control RGP behavior and precise neuronal output remain elusive. Here, we show that the oxidative stress level progressively increases in the developing mouse cortex and regulates RGP behavior and neurogenesis. As development proceeds, numerous gene pathways linked to reactive oxygen species (ROS) and oxidative stress exhibit drastic changes in RGPs. Selective removal of PRDM16, a transcriptional regulator highly expressed in RGPs, elevates ROS level and induces expression of oxidative stress-responsive genes. Coinciding with an enhanced level of oxidative stress, RGP behavior was altered, leading to abnormal deep and superficial layer neuron generation. Simultaneous expression of mitochondrially targeted catalase to reduce cellular ROS levels significantly suppresses cortical defects caused by PRDM16 removal. Together, these findings suggest that oxidative stress actively regulates RGP behavior to ensure proper neurogenesis in the mammalian cortex.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
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Córtex Cerebral
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Estresse Oxidativo
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Proteínas de Ligação a DNA
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Neurogênese
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Células-Tronco Neurais
Limite:
Animals
Idioma:
En
Revista:
Development
Assunto da revista:
BIOLOGIA
/
EMBRIOLOGIA
Ano de publicação:
2020
Tipo de documento:
Article
País de publicação:
ENGLAND
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ESCOCIA
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GB
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GREAT BRITAIN
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INGLATERRA
/
REINO UNIDO
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SCOTLAND
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UK
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UNITED KINGDOM