ZFIN ID: ZDB-PUB-141106-9
Tissue-specific derepression of TCF/LEF controls the activity of the Wnt/β-catenin pathway
Lu, F.I., Sun, Y.H., Wei, C.Y., Thisse, C., Thisse, B.
Date: 2014
Source: Nature communications   5: 5368 (Journal)
Registered Authors: Lu, Fu-I, Sun, Yonghua, Thisse, Bernard, Thisse, Christine, Wei, Changyong
Keywords: Cell signalling, Developmental biology
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*
PubMed: 25371059 Full text @ Nat. Commun.
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.