title: Gli3 repressor controls cell fates and cell adhesion for proper establishment of neurogenic niche.
abstract: Neural stem cells (NSCs) in the subventricular zone (SVZ) rely on environmental signals provided by the neurogenic niche for their proper function. However, little is known about the initial steps of niche establishment, as embryonic radial glia transition to postnatal NSCs. Here, we identify Gli3 repressor (Gli3R), a component of the Sonic hedgehog (Shh) pathway, as a critical factor controlling both cell-type specification and structural organization of the developing SVZ. We demonstrate that Gli3R expressed in radial glia temporally regulates gp130/STAT3 signaling at the transcriptional level to suppress glial characteristics in differentiating ependymal cells. In addition, Gli3R maintains the proper level of Numb in ependymal cells to allow localization of cell adhesion molecules such as vascular cell adhesion molecule (VCAM) and E-cadherin. Thus, our findings reveal a role for Gli3R as a mediator of niche establishment and provide insights into the conditions required for proper SVZ neurogenic niche formation.
authors.affiliation: Program in Genomics of Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Program in Genomics of Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA; Brown-NIH Graduate Partnership Program, Department of Neuroscience, Brown University, Providence, RI 02912, USA.
authors.forename: Anna W
authors.initials: AW
authors.lastname: Kane
authors.affiliation: Program in Genomics of Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Cheol
authors.initials: C
authors.lastname: Lee
authors.affiliation: Program in Genomics of Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: ahnsohyun@mail.nih.gov.
authors.forename: Sohyun
authors.initials: S
authors.lastname: Ahn
mesh_terms: D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000378:metabolism; D002448:Cell Adhesion; D002552:Cerebral Ventricles / Q000166:cytology / Q000196:embryology; D050822:Cytokine Receptor gp130 / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D005904:Glial Fibrillary Acidic Protein; D047908:Intracellular Signaling Peptides and Proteins; D051741:Kruppel-Like Transcription Factors / Q000502:physiology*; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000502:physiology*; D058953:Neural Stem Cells / Q000502:physiology; D055495:Neurogenesis; D050796:STAT3 Transcription Factor / Q000378:metabolism; D055153:Stem Cell Niche; D000074290:Zinc Finger Protein Gli3
chemical_list: D002352:Carrier Proteins; C465571:Gli3 protein, mouse; D005904:Glial Fibrillary Acidic Protein; C494200:Il6st protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D051741:Kruppel-Like Transcription Factors; C454301:Lnx2 protein, mouse; D009419:Nerve Tissue Proteins; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D000074290:Zinc Finger Protein Gli3; C528900:glial fibrillary astrocytic protein, mouse; D050822:Cytokine Receptor gp130