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Publication : Oxidative stress regulates progenitor behavior and cortical neurogenesis.

First Author  Chui A Year  2020
Journal  Development Volume  147
Issue  5 PubMed ID  32041791
Mgi Jnum  J:291489 Mgi Id  MGI:6444562
Doi  10.1242/dev.184150 Citation  Chui A, et al. (2020) Oxidative stress regulates progenitor behavior and cortical neurogenesis. Development 147(5):dev184150
abstractText  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.
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