title: Zbtb20 promotes astrocytogenesis during neocortical development.
abstract: Multipotent neural precursor cells (NPCs) generate astrocytes at late stages of mammalian neocortical development. Many signalling pathways that regulate astrocytogenesis directly induce the expression of GFAP, a marker of terminally differentiated astrocytes. However, astrocyte specification occurs before GFAP expression and essential factors for the specification step have remained elusive. Here we show that Zbtb20 regulates astrocyte specification in the mouse neocortex. Zbtb20 is highly expressed in late-stage NPCs and their astrocytic progeny. Overexpression and knockdown of Zbtb20 promote and suppress astrocytogenesis, respectively, although Zbtb20 does not directly activate the Gfap promoter. Astrocyte induction by Zbtb20 is suppressed by knockdown of Sox9 or NFIA. Furthermore, in the astrocyte lineage, Zbtb20 directly represses the expression of Brn2, which encodes a protein necessary for upper-layer neuron specification. Zbtb20 is thus a key determinant of astrocytogenesis, in which it collaborates with Sox9 and NFIA, and acts in part through direct repression of Brn2 expression.
authors.affiliation: Department of Rehabilitation for the Movement Functions, Research Institute, National Rehabilitation Center for Persons with Disabilities, 4-1 Namiki, Tokorozawa, Saitama 359-8555, Japan.
authors.forename: Motoshi
authors.initials: M
authors.lastname: Nagao
authors.affiliation: Department of Rehabilitation for the Movement Functions, Research Institute, National Rehabilitation Center for Persons with Disabilities, 4-1 Namiki, Tokorozawa, Saitama 359-8555, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Ogata
authors.affiliation: Department of Rehabilitation for the Movement Functions, Research Institute, National Rehabilitation Center for Persons with Disabilities, 4-1 Namiki, Tokorozawa, Saitama 359-8555, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Sawada
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Gotoh
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics*; D018274:Electroporation; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D047468:Immunoprecipitation; D051379:Mice; D051839:NFI Transcription Factors / Q000235:genetics*; D019579:Neocortex / Q000196:embryology* / Q000254:growth & development; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D050809:POU Domain Factors / Q000235:genetics* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055758:SOX9 Transcription Factor / Q000235:genetics*; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D005904:Glial Fibrillary Acidic Protein; D051839:NFI Transcription Factors; D009419:Nerve Tissue Proteins; C497646:Nfia protein, mouse; D050809:POU Domain Factors; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse; D014157:Transcription Factors; C520426:Zbtb20 protein, mouse; C528900:glial fibrillary astrocytic protein, mouse; C074066:Pou3f2 protein, mouse