Gsx2 controls region-specific activation of neural stem cells and injury-induced neurogenesis in the adult subventricular zone

Gsx2 控制成人脑室下区神经干细胞的区域特异性激活和损伤诱导的神经发生

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作者:Alejandro López-Juárez, Jennifer Howard, Kristy Ullom, Lindsey Howard, Andrew Grande, Andrea Pardo, Ronald Waclaw, Yu-Yo Sun, Dianer Yang, Chia-Yi Kuan, Kenneth Campbell, Masato Nakafuku

Abstract

Neural stem cells (NSCs) reside in widespread regions along the lateral ventricle and generate diverse olfactory bulb (OB) interneuron subtypes in the adult mouse brain. Molecular mechanisms underlying their regional diversity, however, are not well understood. Here we show that the homeodomain transcription factor Gsx2 plays a crucial role in the region-specific control of adult NSCs in both persistent and injury-induced neurogenesis. In the intact brain, Gsx2 is expressed in a regionally restricted subset of NSCs and promotes the activation and lineage progression of stem cells, thereby controlling the production of selective OB neuron subtypes. Moreover, Gsx2 is ectopically induced in damaged brains outside its normal expression domains and is required for injury-induced neurogenesis in the subventricular zone (SVZ). These results demonstrate that mobilization of adult NSCs is controlled in a region-specific manner and that distinct mechanisms operate in continuous and injury-induced neurogenesis in the adult brain.

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