title: Gli3 is required for maintenance and fate specification of cortical progenitors.
abstract: Gli3, one of three vertebrate Gli transcription factors in Hedgehog (Hh) pathway, is processed into a repressor form (Gli3R) in the absence of Hh signal and acts as the major negative transducer of the pathway. Although the role of Gli3 in embryonic patterning has been extensively studied, its role in cortical neurogenesis, especially in the regulation of neural progenitors in proliferation and cell fate specification, is largely unknown. To bypass the patterning defects caused by loss of Gli3, we conditionally deleted Gli3 after patterning was complete in mouse. Our results from birthdating and in utero electroporation experiments demonstrate that the Gli3, specifically Gli3R, is critical for specifying the fate of cortical neurons that are generated following a stereotypical temporal order. Moreover, Gli3 is required for maintaining the cortical progenitors in active cell cycle, suggesting that cells may acquire differentiated status as they turn off Gli3 expression during neurogenesis.
authors.affiliation: Unit on Developmental Neurogenetics, Program in Genomics of Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Guannan
authors.initials: G
authors.lastname: Ge
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Uchida
authors.forename: Brian
authors.initials: B
authors.lastname: Luu
authors.forename: Sohyun
authors.initials: S
authors.lastname: Ahn
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D019521:Body Patterning / Q000235:genetics / Q000502:physiology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics; D049109:Cell Proliferation; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D053672:Electrochemotherapy / Q000379:methods; D004622:Embryo, Mammalian; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D018398:Homeodomain Proteins / Q000378:metabolism; D020287:In Situ Nick-End Labeling / Q000379:methods; D007381:Intermediate Filament Proteins / Q000235:genetics; D019394:Ki-67 Antigen / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D064231:Nestin; D058953:Neural Stem Cells / Q000502:physiology*; D009687:Nuclear Proteins / Q000378:metabolism; D011506:Proteins / Q000235:genetics; D022661:RNA, Untranslated; D012097:Repressor Proteins / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D000074290:Zinc Finger Protein Gli3
chemical_list: C511143:Bcl11b protein, mouse; C000624101:Cux1 protein, mouse; C465571:Gli3 protein, mouse; C110853:Gt(ROSA)26Sor non-coding RNA, mouse; D018398:Homeodomain Proteins; D007381:Intermediate Filament Proteins; D019394:Ki-67 Antigen; D051741:Kruppel-Like Transcription Factors; C577484:NES protein, human; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D009687:Nuclear Proteins; D011506:Proteins; D022661:RNA, Untranslated; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins; D000074290:Zinc Finger Protein Gli3; D049452:Green Fluorescent Proteins; D001973:Bromodeoxyuridine