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Drosophila Tcf and Groucho interact to repress Wingless signalling activity
R A Cavallo1, R T Cox, M M Moline
1Department of Biology, University of North Carolina, Chapel Hill 27599, USA.
Abstract:
Wingless/Wnt signalling directs cell-fate choices during embryonic development. Inappropriate reactivation of the pathway causes cancer. In Drosophila, signal transduction from Wingless stabilizes cytosolic Armadillo, which then forms a bipartite transcription factor with the HMG-box protein Drosophila Tcf (dTcf) and activates expression of Wingless-responsive genes. Here we report that in the absence of Armadillo, dTcf acts as a transcriptional repressor of Wingless-responsive genes, and we show that Groucho acts as a corepressor in this process. Reduction of dTcf activity partially suppresses wingless and armadillo mutant phenotypes, leading to derepression of Wingless-responsive genes. Furthermore, overexpression of wild-type dTcf enhances the phenotype of a weak wingless allele. Finally, mutations in the Drosophila groucho gene also suppress wingless and armadillo mutant phenotypes as Groucho physically interacts with dTcf and is required for its full repressor activity.
Insights
Wingless signalling controls cell fate and cancer. In Drosophila, dTcf acts as a repressor of Wingless-responsive genes, with Groucho as a corepressor, revealing new pathway dynamics.
Area of Science:
- Developmental Biology
- Molecular Biology
- Genetics
Background:
- Wingless (Wg)/Wnt signaling is crucial for embryonic development and cell-fate determination.
- Aberrant Wg/Wnt pathway activation is implicated in various cancers.
- In Drosophila, Wg signaling stabilizes Armadillo, forming a transcription factor complex with Drosophila Tcf (dTcf) to activate target genes.
Purpose of the Study:
- To investigate the role of dTcf in Wingless-responsive gene regulation.
- To identify corepressors involved in the Wg/Wnt pathway.
- To elucidate the mechanism of dTcf-mediated transcriptional repression.
Main Methods:
- Genetic analysis of Drosophila mutants for wingless and armadillo.
- Overexpression studies of wild-type dTcf.
- Investigation of the interaction between dTcf and Groucho.
Main Results:
- In the absence of Armadillo, dTcf functions as a transcriptional repressor.
- Groucho acts as a corepressor for dTcf-mediated repression.
- Mutations in the groucho gene suppress wingless and armadillo mutant phenotypes.
- Groucho physically interacts with dTcf and is essential for its repressor activity.
Conclusions:
- Drosophila Tcf (dTcf) functions as a transcriptional repressor in the Wingless pathway, particularly when Armadillo is absent.
- Groucho is a key corepressor that physically interacts with dTcf, mediating its repressor function.
- These findings reveal a dual role for dTcf in Wg/Wnt signaling and highlight the importance of Groucho in transcriptional repression.