title: Signal transducer and activator of transcription-3 maintains the stemness of radial glia at mid-neurogenesis.
abstract: Radial glial cells are stem cell-like populations of glial nature that supply neurons either directly or indirectly via basal progenitors that give rise to neurons. Here we show that signal transducer and activator of transcription-3 (STAT3) signaling, a cytokine signaling mediated by Janus tyrosine kinase (Jak), is active during neurogenesis in radial glia (RG) but not in basal progenitors. Enhanced STAT3 signaling in cortical progenitors caused more RG to persist rather than become neurons. Targeted deletion or RNAi-mediated knockdown of Stat3 resulted in fewer radial glial cells and more basal progenitors and led to premature neurogenesis. The neuronal populations affected in Stat3 mutant mice were the late-born neurons that constitute the upper cortical layers rather than early-born neurons, thus supporting the view that the role of STAT3 at mid-neurogenesis is layer specific. Analysis of dividing RG revealed that STAT3 selectively increased the proportion of dividing RG, whereas downregulation of STAT3 reduced the proportion. Consistent with this, STAT3 activity in dividing RG was associated frequently with vertical cleavage. Pair-cell analysis showed that elevated STAT3 activity correlated with symmetric division of RG, producing more RG, whereas elimination of STAT3 generated more neurogenic cells. Together, our results suggest that STAT3 maintains the stemness of RG and inhibits their transition to basal progenitors at mid-neurogenesis, so probably preserving a pool of RG for later neurogenesis or gliogenesis.
authors.affiliation: School of Life Sciences, BioImaging Research Center and Cell Dynamics Research Center, Gwangju Institute of Science and Technology, Oryong-dong, Buk-gu, Gwangju 500-712, Republic of Korea.
authors.forename: Seulgi
authors.initials: S
authors.lastname: Hong
authors.affiliation: School of Life Sciences, BioImaging Research Center and Cell Dynamics Research Center, Gwangju Institute of Science and Technology, Oryong-dong, Buk-gu, Gwangju 500-712, Republic of Korea msong@gist.ac.kr.
authors.forename: Mi-Ryoung
authors.initials: MR
authors.lastname: Song
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D063928:Ependymoglial Cells / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000502:physiology; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D050796:STAT3 Transcription Factor
keywords: STAT3; neurogenesis; radial glia