LIP-1 phosphatase controls the extent of germline proliferation in Caenorhabditis elegans

EMBO J. 2006 Jan 11;25(1):88-96. doi: 10.1038/sj.emboj.7600901. Epub 2005 Dec 1.

Abstract

Caenorhabditis elegans germline cells are maintained in an undifferentiated and mitotically dividing state by Notch signaling and the FBF (for fem-3 binding factor) RNA-binding protein. Here, we report that the LIP-1 phosphatase, a proposed homolog of mitogen-activated protein (MAP) kinase phosphatases, is required for the normal extent of germline proliferation, and that lip-1 controls germline proliferation by regulating MAP kinase activity. In wild-type germ lines, LIP-1 protein is present in the proximal third of the mitotic region, consistent with its effect on germline proliferation. We provide evidence that lip-1 expression in the germline mitotic region is controlled by a combination of GLP-1/Notch signaling and FBF repression. Unexpectedly, FBF controls the accumulation of lip-1 mRNA, and therefore is likely to control its stability or 3'-end formation. In a sensitized mutant background, LIP-1 can function as a pivotal regulator of the decision between proliferation and differentiation. The control of germline proliferation by LIP-1 has intriguing parallels with the control of stem cells and progenitor cells in vertebrates.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / metabolism
  • Animals
  • Antibodies / immunology
  • Caenorhabditis elegans / enzymology*
  • Caenorhabditis elegans Proteins / genetics*
  • Caenorhabditis elegans Proteins / immunology
  • Caenorhabditis elegans Proteins / metabolism*
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism*
  • Cell Proliferation
  • Chromatin Immunoprecipitation
  • DNA-Binding Proteins / immunology
  • Gene Expression Regulation, Developmental*
  • Germ Cells / enzymology
  • Germ Cells / growth & development*
  • Mitogen-Activated Protein Kinase 1
  • Mitosis
  • Promoter Regions, Genetic
  • Protein Tyrosine Phosphatases / genetics*
  • Protein Tyrosine Phosphatases / metabolism*
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / metabolism
  • Trans-Activators / immunology
  • Transcription Factors

Substances

  • 3' Untranslated Regions
  • Antibodies
  • Caenorhabditis elegans Proteins
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • RNA, Messenger
  • RNA-Binding Proteins
  • SEL-8 protein, C elegans
  • Trans-Activators
  • Transcription Factors
  • fem-3-binding protein, C elegans
  • Protein-Serine-Threonine Kinases
  • Mitogen-Activated Protein Kinase 1
  • mpk-1 protein, C elegans
  • lip-1 protein, C elegans
  • Protein Tyrosine Phosphatases