title: The transcription factor Gli3 regulates differentiation of fetal CD4- CD8- double-negative thymocytes.
abstract: Glioblastoma 3 (Gli3) is a transcription factor involved in patterning and oncogenesis. Here, we demonstrate a role for Gli3 in thymocyte development. Gli3 is differentially expressed in fetal CD4- CD8- double-negative (DN) thymocytes and is most highly expressed at the CD44+ CD25- DN (DN1) and CD44- CD25- (DN4) stages of development but was not detected in adult thymocytes. Analysis of null mutants showed that Gli3 is involved at the transitions from DN1 to CD44+ CD25+ DN (DN2) cell and from DN to CD4+ CD8+ double-positive (DP) cell. Gli3 is required for differentiation from DN to DP thymocyte, after pre-T-cell receptor (TCR) signaling but is not necessary for pre-TCR-induced proliferation or survival. The effect of Gli3 was dose dependent, suggesting its direct involvement in the transcriptional regulation of genes controlling T-cell differentiation during fetal development.
authors.affiliation: Division of Cell and Molecular Biology, Faculty of Life Sciences, Imperial College London, Sir Alexander Fleming Bldg, South Kensington Campus, London SW7 2AZ, United Kingdom.
authors.forename: Ariadne L
authors.initials: AL
authors.lastname: Hager-Theodorides
authors.forename: Johannes T
authors.initials: JT
authors.lastname: Dessens
authors.forename: Susan V
authors.initials: SV
authors.lastname: Outram
authors.forename: Tessa
authors.initials: T
authors.lastname: Crompton
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000032:analysis*; D015704:CD4 Antigens; D016827:CD8 Antigens; D002454:Cell Differentiation; D019070:Cell Lineage; D004268:DNA-Binding Proteins / Q000502:physiology*; D004622:Embryo, Mammalian / Q000166:cytology / Q000276:immunology; D018507:Gene Expression Regulation, Developmental; D051741:Kruppel-Like Transcription Factors; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009419:Nerve Tissue Proteins / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology*; D013950:Thymus Gland / Q000166:cytology* / Q000196:embryology / Q000254:growth & development; D014157:Transcription Factors / Q000502:physiology*; D000074290:Zinc Finger Protein Gli3
chemical_list: D015703:Antigens, CD; D015704:CD4 Antigens; D016827:CD8 Antigens; D004268:DNA-Binding Proteins; C465571:Gli3 protein, mouse; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; D000074290:Zinc Finger Protein Gli3