title: Rbf Regulates Drosophila Spermatogenesis via Control of Somatic Stem and Progenitor Cell Fate in the Larval Testis.
abstract: The Drosophila testis has been fundamental to understanding how stem cells interact with their endogenous microenvironment, or niche, to control organ growth in vivo. Here, we report the identification of two independent alleles for the highly conserved tumor suppressor gene, Retinoblastoma-family protein (Rbf), in a screen for testis phenotypes in X chromosome third-instar lethal alleles. Rbf mutant alleles exhibit overproliferation of spermatogonial cells, which is phenocopied by the molecularly characterized Rbf11null allele. We demonstrate that Rbf promotes cell-cycle exit and differentiation of the somatic and germline stem cells of the testes. Intriguingly, depletion of Rbf specifically in the germline does not disrupt stem cell differentiation, rather Rbf loss of function in the somatic lineage drives overproliferation and differentiation defects in both lineages. Together our observations suggest that Rbf in the somatic lineage controls germline stem cell renewal and differentiation non-autonomously via essential roles in the microenvironment of the germline lineage.
authors.affiliation: Centre for Stem Cell Systems, Department of Anatomy and Neuroscience, The University of Melbourne, Melbourne, VIC 3010, Australia; Department of Anatomy and Neuroscience, The University of Melbourne, Melbourne, VIC 3010, Australia.
authors.forename: Nicole
authors.initials: N
authors.lastname: Dominado
authors.affiliation: Department of Genetics, La Trobe University, Melbourne, VIC 3086, Australia.
authors.forename: John E
authors.initials: JE
authors.lastname: La Marca
authors.affiliation: Centre for Stem Cell Systems, Department of Anatomy and Neuroscience, The University of Melbourne, Melbourne, VIC 3010, Australia; Department of Anatomy and Neuroscience, The University of Melbourne, Melbourne, VIC 3010, Australia.
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Siddall
authors.affiliation: Centre for Stem Cell Systems, Department of Anatomy and Neuroscience, The University of Melbourne, Melbourne, VIC 3010, Australia; Department of Anatomy and Neuroscience, The University of Melbourne, Melbourne, VIC 3010, Australia.
authors.forename: James
authors.initials: J
authors.lastname: Heaney
authors.affiliation: Department of Anatomy and Neuroscience, The University of Melbourne, Melbourne, VIC 3010, Australia.
authors.forename: Mai
authors.initials: M
authors.lastname: Tran
authors.affiliation: Temasek Life Sciences Laboratory, National University of Singapore, Singapore 117543, Singapore; Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore.
authors.forename: Yu
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Temasek Life Sciences Laboratory, National University of Singapore, Singapore 117543, Singapore.
authors.forename: Fengwei
authors.initials: F
authors.lastname: Yu
authors.affiliation: Neuroscience & Behavioral Disorder Program, Duke-National University of Singapore, Singapore 169857, Singapore; Department of Physiology, National University of Singapore, Singapore 117597, Singapore.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Genetics, La Trobe University, Melbourne, VIC 3086, Australia.
authors.forename: W Gregory
authors.initials: WG
authors.lastname: Somers
authors.affiliation: Department of Anatomy and Neuroscience, The University of Melbourne, Melbourne, VIC 3010, Australia; The John Curtin School of Medical Research, The Australian National University, Acton, ACT 2601, Australia. Electronic address: l.quinn@unimelb.edu.au.
authors.forename: Leonie M
authors.initials: LM
authors.lastname: Quinn
authors.affiliation: Centre for Stem Cell Systems, Department of Anatomy and Neuroscience, The University of Melbourne, Melbourne, VIC 3010, Australia; Department of Anatomy and Neuroscience, The University of Melbourne, Melbourne, VIC 3010, 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; D019070:Cell Lineage; D049109:Cell Proliferation; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000378:metabolism*; D005854:Germ Cells / Q000166:cytology / Q000378:metabolism; D007814:Larva; D008297:Male; D009154:Mutation / Q000235:genetics; D016160:Retinoblastoma Protein / Q000378:metabolism*; D013091:Spermatogenesis; D055153:Stem Cell Niche; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D013737:Testis / Q000166:cytology*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; C099965:Rbf protein, Drosophila; D016160:Retinoblastoma Protein; D014157:Transcription Factors
keywords: Drosophila; germline; proliferation; retinoblastoma protein; self-renewal; stem cell; stem cell niche; testis