Multi-pathway control of the proliferation versus meiotic development decision in the Caenorhabditis elegans germline

Dev Biol. 2004 Apr 15;268(2):342-57. doi: 10.1016/j.ydbio.2003.12.023.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Biomarkers
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / immunology
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / immunology
  • Cell Division / physiology
  • Germ Cells / immunology
  • Germ Cells / physiology*
  • Glucagon / metabolism
  • Glucagon-Like Peptide 1
  • Meiosis / physiology*
  • Mitosis / physiology*
  • Neoplasms / metabolism
  • Peptide Fragments / metabolism
  • Phosphoproteins / immunology
  • Protein Precursors / metabolism
  • Schizosaccharomyces pombe Proteins / immunology
  • Signal Transduction / physiology


  • Biomarkers
  • Caenorhabditis elegans Proteins
  • HIM-3 protein, C elegans
  • Peptide Fragments
  • Phosphoproteins
  • Protein Precursors
  • Schizosaccharomyces pombe Proteins
  • REC8 protein, S pombe
  • Glucagon-Like Peptide 1
  • Glucagon