Tissue-specific derepression of TCF/LEF controls the activity of the Wnt/β-catenin pathway

Nat Commun. 2014 Nov 5;5:5368. doi: 10.1038/ncomms6368.

Abstract

Upon stimulation by Wnt ligands, the canonical Wnt/β-catenin signalling pathway results in the stabilization of β-catenin and its translocation into the nucleus to form transcriptionally active complexes with sequence-specific DNA-binding T-cell factor/lymphoid enhancer factor (TCF/LEF) family proteins. In the absence of nuclear β-catenin, TCF proteins act as transcriptional repressors by binding to Groucho/Transducin-Like Enhancer of split (TLE) proteins that function as co-repressors by interacting with histone deacetylases whose activity leads to the generation of transcriptionally silent chromatin. Here we show that the transcription factor Ladybird homeobox 2 (Lbx2) positively controls the Wnt/β-catenin signalling pathway in the posterior lateral and ventral mesoderm of the zebrafish embryo at the gastrula stage, by directly interfering with the binding of Groucho/TLE to TCF, thereby preventing formation of transcription repressor complexes. These findings reveal a novel level of regulation of the canonical Wnt/β-catenin signalling pathway occurring in the nucleus and involving tissue-specific derepression of TCF by Lbx2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Co-Repressor Proteins / metabolism
  • Cytoskeletal Proteins / metabolism*
  • Gastrula / metabolism
  • Mesoderm / metabolism*
  • Repressor Proteins / physiology*
  • Signal Transduction
  • Transcription Factor 7-Like 1 Protein / metabolism*
  • Wnt Proteins / metabolism*
  • Zebrafish
  • Zebrafish Proteins / metabolism*
  • Zebrafish Proteins / physiology*
  • beta Catenin / metabolism*

Substances

  • Co-Repressor Proteins
  • Cytoskeletal Proteins
  • Lbx2 protein, zebrafish
  • Repressor Proteins
  • Transcription Factor 7-Like 1 Protein
  • Wnt Proteins
  • Zebrafish Proteins
  • beta Catenin
  • tle3a protein, zebrafish
  • wnt8a protein, zebrafish