title: The miRNA pathway intrinsically controls self-renewal of Drosophila germline stem cells.
abstract: Stem cells uniquely self-renew and maintain tissue homoeostasis by differentiating into different cell types to replace aged or damaged cells [1]. During oogenesis of Drosophila melanogaster, self-renewal of germline stem cells (GSCs) requires both intrinsic signaling mechanisms and extrinsic signals from neighboring niche cells [2]. Emerging evidence suggests that microRNA (miRNA)-mediated translational regulation may also control Drosophila GSC self-renewal [3, 4]. It is unclear, however, whether the miRNA pathway functions within stem cells or niche cells to maintain GSCs. In Drosophila, Dicer-1 (Dcr-1) and the double-stranded RNA binding protein Loquacious (Loqs) catalyze miRNA biogenesis [3-5]. Here, we generate loqs knockout (loqs(KO)) flies by ends-out homologous recombination and show that loqs is essential for embryonic viability and ovarian GSC maintenance. Both developmental and miRNA processing defects are rescued by transgenic expression of Loqs-PB, but not Loqs-PA. Furthermore, mosaic germline analysis indicates that Loqs is required intrinsically for GSC maintenance. Consistently, GSCs are restored in loqs mutant ovaries by germline expression, but not somatic expression, of Loqs-PB. Together, these results demonstrate that Loqs-PB, but not Loqs-PA, is necessary and sufficient for Drosophila development and the miRNA pathway. Our study strongly suggests that miRNAs play an intrinsic, but not extrinsic, role in Drosophila female GSC self-renewal.
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390.
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Park
authors.forename: Xiang
authors.initials: X
authors.lastname: Liu
authors.forename: Tamara J
authors.initials: TJ
authors.lastname: Strauss
authors.forename: Dennis M
authors.initials: DM
authors.lastname: McKearin
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Liu
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified / Q000254:growth & development / Q000378:metabolism; D002454:Cell Differentiation; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D005260:Female; D035683:MicroRNAs / Q000502:physiology*; D009866:Oogenesis / Q000235:genetics / Q000502:physiology; D010063:Ovum / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D016601:RNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; C503213:Loqs protein, Drosophila; D035683:MicroRNAs; D020033:Protein Isoforms; D016601:RNA-Binding Proteins