C. elegans TCF protein, POP-1, converts from repressor to activator as a result of Wnt-induced lowering of nuclear levels

Dev Biol. 2005 Sep 15;285(2):584-92. doi: 10.1016/j.ydbio.2005.07.008.

Abstract

Canonical Wnt signaling converts the TCF/LEF transcription factor from repressor to activator by increasing nuclear levels of its coactivator, beta-catenin. A striking exception had been reported for Wnt-induced endoderm formation during C. elegans embryogenesis. It has long been believed that transcriptional activation of Wnt target genes in the endoderm precursor occurred due to a lowering of nuclear levels of the worm TCF/LEF protein, POP-1, effectively alleviating POP-1 repressive activity. Contrary to this model, we demonstrate here that POP-1 directly activates Wnt target genes in the endoderm precursor. Wnt converts POP-1 from a repressor to an activator, and this conversion requires that POP-1 nuclear levels be lowered in the endoderm precursor. We propose that the balance between TCF/LEF and coactivator(s), achieved by elevating coactivator levels (the canonical pathway) and/or reducing TCF/LEF levels (worm endoderm), determines Wnt signal strength.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / embryology*
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • DNA-Binding Proteins / metabolism*
  • Endoderm / physiology*
  • Gene Expression Regulation / physiology*
  • Genetic Markers / genetics
  • High Mobility Group Proteins / metabolism*
  • Microscopy, Fluorescence
  • Plasmids / genetics
  • Signal Transduction / genetics
  • Signal Transduction / physiology*
  • Wnt Proteins / metabolism*

Substances

  • Caenorhabditis elegans Proteins
  • DNA-Binding Proteins
  • Genetic Markers
  • High Mobility Group Proteins
  • Wnt Proteins
  • pop-1 protein, C elegans