FGF signalling modulates transcriptional repression by Xenopus groucho-related-4.
BACKGROUND
Developmental cell signals co-operate in the processes of cell specification and tissue patterning during embryogenesis. Interactions between the FGF (fibroblast growth factor) and Wnt signalling pathways have been demonstrated in a number of developmental processes, including mesoderm formation in amphibian embryos. However, the mechanism underlying the interactions between these key signalling pathways remains unclear.


RESULTS
In the present study, we find that the ability of TLE4/Xgrg4 (transducin-like enhancer of split 4/Xenopus groucho-related gene 4) to inhibit a transcriptional target of canonical Wnt signalling is reduced in the presence of FGF and that this is partially dependent on a consensus site for MAPK (mitogen-activated protein kinase) phosphorylation in TLE4/Xgrg4.


CONCLUSIONS
These data suggest to us a novel molecular mechanism where FGF and Wnt signalling pathways interact at the level of the co-repressor TLE4/Xgrg4: the weakening of TLE4/Xgrg4 repression by FGF signalling, combined with the stabilization of beta-catenin by Wnt signals, enhances expression of Wnt target genes.
Burks
Patrick J
PJ
Biology Department, University of York, York YO10 5YW, U.K.
Isaacs
Harry V
HV
Pownall
Mary E
ME
D000818:Animals; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000235:genetics* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D014981:Xenopus / Q000196:embryology*; D029867:Xenopus Proteins / Q000235:genetics* / Q000378:metabolism
D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; D012097:Repressor Proteins; C523700:TLE4 protein, Xenopus; D051153:Wnt Proteins; D029867:Xenopus Proteins; D005346:Fibroblast Growth Factors; D020928:Mitogen-Activated Protein Kinases