title: Drosophila TGIF is essential for developmentally regulated transcription in spermatogenesis.
abstract: We have investigated the role of TGIF, a TALE-class homeodomain transcription factor, in Drosophila development. In vertebrates, TGIF has been implicated, by in vitro analysis, in several pathways, most notably as a repressor modulating the response to TGFbeta signalling. Human TGIF has been associated with the developmental disorder holoprosencephaly. Drosophila TGIF is represented by the products of two tandemly repeated highly similar genes, achintya and vismay. We have generated mutations that delete both genes. Homozygous mutant flies are viable and appear morphologically normal, but the males are completely sterile. The defect lies at the primary spermatocyte stage and differentiation is blocked prior to the onset of the meiotic divisions. We show that mutants lacking TGIF function fail to activate transcription of many genes required for sperm manufacture and of some genes required for entry into the meiotic divisions. This groups TGIF together with two other genes producing similar phenotypes, always early and cookie monster, as components of the machinery required for the activation of the spermatogenic programme of transcription. TGIF is the first sequence-specific transcription factor identified in this pathway. By immunolabelling in mouse testes we show that TGIF is expressed in the early stages of spermatogenesis consistent with a conserved role in the activation of the spermatogenesis transcription programme.
authors.affiliation: Department of Anatomy, University of Cambridge, Downing Street, Cambridge, CB2 3DY, UK.
authors.forename: Savita
authors.initials: S
authors.lastname: Ayyar
authors.forename: Jianqiao
authors.initials: J
authors.lastname: Jiang
authors.forename: Anna
authors.initials: A
authors.lastname: Collu
authors.forename: Helen
authors.initials: H
authors.lastname: White-Cooper
authors.forename: Robert A H
authors.initials: RA
authors.lastname: White
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development* / Q000502:physiology; D017353:Gene Deletion; D005801:Genes, Homeobox; D006801:Humans; D007248:Infertility, Male; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D010641:Phenotype; D016415:Sequence Alignment; D013091:Spermatogenesis / Q000502:physiology*; D013737:Testis / Q000166:cytology / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; C476930:achi protein, Drosophila; C418886:aly protein, Drosophila; C471972:comr protein, Drosophila