Open AccessOxidative stress regulates progenitor behavior and cortical neurogenesis
Author(s) -
Angela Chui,
Qiangqiang Zhang,
Qigen Dai,
Song-Hai Shi
Publication year - 2020
Publication title -
development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.754
H-Index - 325
eISSN - 1477-9129
pISSN - 0950-1991
DOI - 10.1242/dev.184150
Subject(s) - neurogenesis , oxidative stress , biology , microbiology and biotechnology , reactive oxygen species , cerebral cortex , cortex (anatomy) , catalase , progenitor cell , oxidative phosphorylation , neuroscience , stem cell , biochemistry
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.