title: HOW is required for stem cell maintenance in the Drosophila testis and for the onset of transit-amplifying divisions.
abstract: The mechanisms by which germline stem cells (GSCs) in the Drosophila testis undergo asymmetric division to regenerate a stem cell as well as a daughter (gonialblast) that will only undergo a further four mitotic divisions prior to entering premeiotic S phase and differentiating into a cyst of spermatocytes are not fully resolved. Here we demonstrate that the HOW RNA-binding protein is required for maintenance of CycB and therefore mitotic progression in GSCs and gonialblasts as well as determining the timing of the spermatogonial divisions. HOW is normally expressed in a complementary pattern to Bam in the germline and bam mRNA is bound by HOW in vivo. Ectopic expression of the HOW(L) isoform is associated with a delay in accumulation of Bam to the level required for differentiation, resulting in extra mitotic divisions. Spatiotemporal regulation of HOW expression is therefore required to specify the four spermatogonial transit-amplifying divisions.
authors.affiliation: Department of Anatomy and Cell Biology, University of Melbourne, Parkville, Victoria 3010, Australia; ARC Centre of Excellence in Biotechnology and Development, Callaghan, NSW 2308, Australia.
authors.forename: Adrian C
authors.initials: AC
authors.lastname: Monk
authors.affiliation: Department of Anatomy and Cell Biology, University of Melbourne, Parkville, Victoria 3010, Australia; ARC Centre of Excellence in Biotechnology and Development, Callaghan, NSW 2308, Australia.
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Siddall
authors.affiliation: Department of Molecular Genetics, Weizmann Institute, Reohovat 76100, Israel.
authors.forename: Talila
authors.initials: T
authors.lastname: Volk
authors.affiliation: ARC Centre of Excellence in Biotechnology and Development, Callaghan, NSW 2308, Australia; School of Environmental & Life Sciences, University of Newcastle, Callaghan, NSW 2308, Australia.
authors.forename: Barbara
authors.initials: B
authors.lastname: Fraser
authors.affiliation: Department of Anatomy and Cell Biology, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Leonie M
authors.initials: LM
authors.lastname: Quinn
authors.affiliation: ARC Centre of Excellence in Biotechnology and Development, Callaghan, NSW 2308, Australia; School of Environmental & Life Sciences, University of Newcastle, Callaghan, NSW 2308, Australia.
authors.forename: Eileen A
authors.initials: EA
authors.lastname: McLaughlin
authors.affiliation: Department of Anatomy and Cell Biology, University of Melbourne, Parkville, Victoria 3010, Australia; ARC Centre of Excellence in Biotechnology and Development, Callaghan, NSW 2308, Australia. Electronic address: g.hime@unimelb.edu.au.
authors.forename: Gary R
authors.initials: GR
authors.lastname: Hime
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D049109:Cell Proliferation; D048429:Cell Size; D019926:Cyclin B / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000378:metabolism; D016195:G2 Phase; D008297:Male; D008938:Mitosis; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000378:metabolism*; D009928:Organ Specificity; D016601:RNA-Binding Proteins / Q000378:metabolism*; D013094:Spermatozoa / Q000166:cytology / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D013737:Testis / Q000166:cytology* / Q000378:metabolism*; D013997:Time Factors
chemical_list: D019926:Cyclin B; D029721:Drosophila Proteins; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; C091674:bam protein, Drosophila; C106296:how protein, Drosophila