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