title: Tissue-specific derepression of TCF/LEF controls the activity of the Wnt/β-catenin pathway.
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.
authors.affiliation: 1] Department of Cell Biology, University of Virginia, Charlottesville, Virginia 22908, USA [2] Institute of Biotechnology, National Cheng Kung University, Tainan City 701, Taiwan.
authors.forename: Fu-I
authors.initials: FI
authors.lastname: Lu
authors.affiliation: 1] Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/Université de Strasbourg, 1 rue Laurent Fries, BP.10142, Illkirch 67400, France [2] State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China.
authors.forename: Yong-Hua
authors.initials: YH
authors.lastname: Sun
authors.affiliation: 1] State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China [2] University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Chang-Yong
authors.initials: CY
authors.lastname: Wei
authors.affiliation: 1] Department of Cell Biology, University of Virginia, Charlottesville, Virginia 22908, USA [2] Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/Université de Strasbourg, 1 rue Laurent Fries, BP.10142, Illkirch 67400, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Thisse
authors.affiliation: 1] Department of Cell Biology, University of Virginia, Charlottesville, Virginia 22908, USA [2] Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/Université de Strasbourg, 1 rue Laurent Fries, BP.10142, Illkirch 67400, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Thisse
mesh_terms: D000818:Animals; D056970:Co-Repressor Proteins / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D005775:Gastrula / Q000378:metabolism; D008648:Mesoderm / Q000378:metabolism*; D012097:Repressor Proteins / Q000502:physiology*; D015398:Signal Transduction; D058125:Transcription Factor 7-Like 1 Protein / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000378:metabolism* / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D056970:Co-Repressor Proteins; D003598:Cytoskeletal Proteins; C540766:Lbx2 protein, zebrafish; D012097:Repressor Proteins; D058125:Transcription Factor 7-Like 1 Protein; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; C000604108:tle3a protein, zebrafish; C094521:wnt8a protein, zebrafish