Gsx2 controls region-specific activation of neural stem cells and injury-induced neurogenesis in the adult subventricular zone
- Alejandro López-Juárez1,
- Jennifer Howard1,
- Kristy Ullom1,
- Lindsey Howard1,
- Andrew Grande1,2,6,
- Andrea Pardo1,7,
- Ronald Waclaw1,3,4,
- Yu-Yo Sun1,8,
- Dianer Yang1,8,
- Chia-Yi Kuan1,4,8,
- Kenneth Campbell1,2,4,5 and
- Masato Nakafuku1,2,4,9
- 1Division of Developmental Biology, Cincinnati Children's Hospital Research Foundation, Cincinnati, Ohio 45229, USA;
- 2Department of Neurosurgery, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA;
- 3Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Research Foundation, Cincinnati, Ohio 45229, USA;
- 4Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA;
- 5Division of Neurosurgery, Cincinnati Children's Hospital Research Foundation, Cincinnati, Ohio 45229, USA
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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Footnotes
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↵9 Corresponding author
E-mail masato.nakafuku{at}cchmc.org
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Supplemental material is available for this article.
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Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.217539.113.
- Received March 10, 2013.
- Accepted May 3, 2013.
- Copyright © 2013 by Cold Spring Harbor Laboratory Press