LIN-12/Notch activation leads to microRNA-mediated down-regulation of Vav in C. elegans

Science. 2005 Nov 25;310(5752):1330-3. doi: 10.1126/science.1119481. Epub 2005 Oct 20.

Abstract

Cell-cell interactions and cross-talk between signaling pathways specify Caenorhabditis elegans vulval precursor cells (VPCs) to adopt a spatial pattern: a central "1 degrees " VPC, in which epidermal growth factor receptor (EGFR)-mitogen-activated protein kinase (MAPK) activity is high and LIN-12/Notch activity is low, flanked by two "2 degrees " VPCs, in which LIN-12/Notch activity is high and EGFR-MAPK activity is low. Here, we identify a microRNA gene, mir-61, as a direct transcriptional target of LIN-12 and show that expression of mir-61 promotes the 2 degrees fate. We also identify vav-1, the ortholog of the Vav oncogene, as a target of mir-61, and show that down-regulation of VAV-1 promotes lin-12 activity in specifying the 2 degrees fate. Our results suggest that lin-12, mir-61, and vav-1 form a feedback loop that helps maximize lin-12 activity in the presumptive 2 degrees VPCs.

Publication types

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

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Animals, Genetically Modified
  • Caenorhabditis elegans / cytology*
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / growth & development
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / genetics*
  • Caenorhabditis elegans Proteins / metabolism*
  • Computational Biology
  • Down-Regulation
  • Feedback, Physiological
  • Female
  • Gene Expression Regulation, Developmental
  • Genes, Helminth
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism*
  • Proto-Oncogene Proteins c-vav / genetics*
  • Proto-Oncogene Proteins c-vav / metabolism
  • Receptors, Notch
  • Regulatory Sequences, Nucleic Acid
  • Signal Transduction
  • Stem Cells / cytology*
  • Stem Cells / metabolism
  • Transcription, Genetic
  • Vulva / cytology
  • Vulva / growth & development

Substances

  • 3' Untranslated Regions
  • Caenorhabditis elegans Proteins
  • Lin-12 protein, C elegans
  • Membrane Proteins
  • MicroRNAs
  • Proto-Oncogene Proteins c-vav
  • Receptors, Notch
  • VAV-1 protein, C elegans