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

Dave Hansen, E. Jane Albert Hubbard, Tim Schedl

Research output: Contribution to journalArticlepeer-review

113 Scopus citations

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.

Original languageEnglish
Pages (from-to)342-357
Number of pages16
JournalDevelopmental Biology
Volume268
Issue number2
DOIs
StatePublished - Apr 15 2004

Keywords

  • GLP-1/Notch
  • Germline development
  • Germline tumor
  • Meiotic entry
  • Proliferation
  • gld-1
  • gld-2
  • nos-3

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