title: The microRNA pathway controls germ cell proliferation and differentiation in C. elegans.
abstract: The discovery of the miRNA pathway revealed a new layer of molecular control of biological processes. To uncover new functions of this gene regulatory pathway, we undertook the characterization of the two miRNA-specific Argonaute proteins in Caenorhabditis elegans, ALG-1 and ALG-2. We first observed that the loss-of-function of alg-1 and alg-2 genes resulted in reduced progeny number. An extensive analysis of the germline of these mutants revealed a reduced mitotic region, indicating fewer proliferating germ cells. We also observed an early entry into meiosis in alg-1 and alg-2 mutant animals. We detected ALG-1 and ALG-2 protein expressions in the distal tip cell (DTC), a specialized cell located at the tip of both C. elegans gonadal arms that regulates mitosis-meiosis transition. Re-establishing the expression of alg-1 specifically in the DTC of mutant animals partially rescued the observed germline defects. Further analyses also support the implication of the miRNA pathway in gametogenesis. Interestingly, we observed that disruption of five miRNAs expressed in the DTC led to similar phenotypes. Finally, gene expression analysis of alg-1 mutant gonads suggests that the miRNA pathway is involved in the regulation of different pathways important for germline proliferation and differentiation. Collectively, our data indicate that the miRNA pathway plays a crucial role in the control of germ cell biogenesis in C. elegans.
authors.affiliation: Laval University Cancer Research Centre, Hôtel-Dieu de Québec (CHUQ), Quebec City, Québec, Canada G1R 2J6.
authors.forename: Syed Irfan Ahmad
authors.initials: SI
authors.lastname: Bukhari
authors.forename: Alejandro
authors.initials: A
authors.lastname: Vasquez-Rifo
authors.forename: Dominic
authors.initials: D
authors.lastname: Gagné
authors.forename: Eric R
authors.initials: ER
authors.lastname: Paquet
authors.forename: Monique
authors.initials: M
authors.lastname: Zetka
authors.forename: Claude
authors.initials: C
authors.lastname: Robert
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Masson
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Simard
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000254:growth & development / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D005854:Germ Cells / Q000166:cytology* / Q000378:metabolism; D006066:Gonads / Q000166:cytology; D008540:Meiosis; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008938:Mitosis; D009154:Mutation; D009865:Oocytes / Q000378:metabolism; D010641:Phenotype; D034622:RNA Interference; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C558782:ALG-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D035683:MicroRNAs; D016601:RNA-Binding Proteins