title: Multi-pathway control of the proliferation versus meiotic development decision in the Caenorhabditis elegans germline.
abstract: An important event in the development of the germline is the initiation of meiotic development. In Caenorhabditis elegans, the conserved GLP-1/Notch signaling pathway regulates the proliferative versus meiotic entry decision, at least in part, by spatially inhibiting genes in the gld-1 and gld-2 parallel pathways, which are proposed to either inhibit proliferation and/or promote meiotic development. Mutations that cause constitutive activation of the GLP-1 pathway, or inactivation of both the gld-1 and gld-2 parallel pathways, result in a tumorous germline in which all cells are thought to be proliferative. Here, to analyze proliferation and meiotic entry in wild-type and mutant tumorous germlines, we use anti-REC-8 and anti-HIM-3 specific antibodies as markers, which under our fixation conditions, stain proliferative and meiotic cells, respectively. Using these makers in wild-type animals, we find that the border of the switch from proliferation to meiotic entry is staggered in late-larval and adult germlines. In wild-type adults, the switch occurs between 19 and 26 cell diameters from the distal end, on average. Our analysis of mutants reveals that tumorous germlines that form when GLP-1 is constitutively active are completely proliferative, while tumors due to inactivation of the gld-1 and gld-2 pathways show evidence of meiotic entry. Genetic and time course studies suggest that a third pathway may exist, parallel to the GLD-1 and GLD-2 pathways, that promotes meiotic development.
authors.affiliation: Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Dave
authors.initials: D
authors.lastname: Hansen
authors.forename: E Jane Albert
authors.initials: EJ
authors.lastname: Hubbard
authors.forename: Tim
authors.initials: T
authors.lastname: Schedl
mesh_terms: D000818:Animals; D015415:Biomarkers; D017173:Caenorhabditis elegans / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000276:immunology; D002455:Cell Division / Q000502:physiology; D005854:Germ Cells / Q000276:immunology / Q000502:physiology*; D005934:Glucagon / Q000378:metabolism; D052216:Glucagon-Like Peptide 1; D008540:Meiosis / Q000502:physiology*; D008938:Mitosis / Q000502:physiology*; D009369:Neoplasms / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D010750:Phosphoproteins / Q000276:immunology; D011498:Protein Precursors / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000276:immunology; D015398:Signal Transduction / Q000502:physiology; D000097722:Cohesins
chemical_list: D015415:Biomarkers; D029742:Caenorhabditis elegans Proteins; D005934:Glucagon; D052216:Glucagon-Like Peptide 1; D010446:Peptide Fragments; D010750:Phosphoproteins; D011498:Protein Precursors; D029702:Schizosaccharomyces pombe Proteins; C121599:HIM-3 protein, C elegans; C077081:REC8 protein, S pombe; D000097722:Cohesins