title: Gsx2 controls region-specific activation of neural stem cells and injury-induced neurogenesis in the adult subventricular zone.
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.
authors.affiliation: Division of Developmental Biology, Cincinnati Children's Hospital Research Foundation, Cincinnati, Ohio 45229, USA.
authors.forename: Alejandro
authors.initials: A
authors.lastname: López-Juárez
authors.forename: Jennifer
authors.initials: J
authors.lastname: Howard
authors.forename: Kristy
authors.initials: K
authors.lastname: Ullom
authors.forename: Lindsey
authors.initials: L
authors.lastname: Howard
authors.forename: Andrew
authors.initials: A
authors.lastname: Grande
authors.forename: Andrea
authors.initials: A
authors.lastname: Pardo
authors.forename: Ronald
authors.initials: R
authors.lastname: Waclaw
authors.forename: Yu-Yo
authors.initials: YY
authors.lastname: Sun
authors.forename: Dianer
authors.initials: D
authors.lastname: Yang
authors.forename: Chia-Yi
authors.initials: CY
authors.lastname: Kuan
authors.forename: Kenneth
authors.initials: K
authors.lastname: Campbell
authors.forename: Masato
authors.initials: M
authors.lastname: Nakafuku
mesh_terms: D053687:Adult Stem Cells / Q000378:metabolism; D000818:Animals; D019070:Cell Lineage; D018398:Homeodomain Proteins / Q000378:metabolism*; D020547:Lateral Ventricles / Q000166:cytology* / Q000293:injuries* / Q000378:metabolism; D051379:Mice; D058953:Neural Stem Cells / Q000145:classification / Q000166:cytology* / Q000378:metabolism*; D055495:Neurogenesis; D009830:Olfactory Bulb / Q000166:cytology; D009928:Organ Specificity; D055153:Stem Cell Niche; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C109498:Gsh2 protein, mouse; D018398:Homeodomain Proteins; D014157:Transcription Factors
keywords: adult neurogenesis; injury; regional identity; stem cell; stroke