DROSOPHILA TCF AND GROUCHO INTERACT TO REPRESS WINGLESS SIGNALING ACTIVITY

Wingless/Wnt signalling directs cell-fate choices during embryonic dev elopment(1,2). Inappropriate reactivation of the pathway causes cancer (3-5). In Drosophila, signal transduction from Wingless stabilizes cyt osolic Armadillo(1), which then forms a bipartite transcription factor with the HMG-box protein Drosophila Tcf (dTcf) and activates expressi on of Wingless-responsive genes(6-8) Here we report that in the absenc e of Armadillo, dTcf acts as a transcriptional repressor of Wingless-r esponsive genes, and we show that Groucho acts as a corepressor in thi s process. Reduction of dTcf activity partially suppresses wingless an d armadillo mutant phenotypes, leading to derepression of Wingless-res ponsive genes. Furthermore, overexpression of wild-type dTcf enhances the phenotype of a weak wingless allele. Finally, mutations in the Dro sophila groucho gene also suppress wingless and armadillo mutant pheno types as Groucho physically interacts with dTcf and is required for it s full repressor activity.