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

Fu I. Lu, Yong Hua Sun, Chang Yong Wei, Christine Thisse, Bernard Thisse

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)

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.

Original languageEnglish
Article number5368
JournalNature communications
Volume5
DOIs
Publication statusPublished - 2015 Feb

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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