Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Drosophila Tcf and Groucho interact to repress Wingless signalling activity

Nature volume 395, pages 604–608 (1998)Cite this article

Abstract

Wingless/Wnt signalling directs cell-fate choices during embryonic development1,2. Inappropriate reactivation of the pathway causes cancer3,4,5. In Drosophila, signal transduction from Wingless stabilizes cytosolic Armadillo1, which then forms a bipartite transcription factor with the HMG-box protein Drosophila Tcf (dTcf) and activates expression of Wingless-responsive genes6,7,8. 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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: dTcf is a dose-dependent suppressor of wg and arm.
Figure 2: dTcf represses Wg-responsive genes.
Figure 3: dTcf interacts with Drosophila Gro.
Figure 4: Gro acts together with dTcf to repress Wg-responsive genes.

Similar content being viewed by others

References

  1. Cadigan, K. M. & Nusse, R. Wnt signaling: a common theme in animal development. Genes Dev. 11, 3286–3305 (1997).

    Article  CAS  Google Scholar 

  2. Bejsovec, A. & Peifer, M. The wingless/Wnt-1 signaling pathway — new insights into the cellular mechanisms of signal transduction. Adv. Dev. Biochem. 4, 1–45 (1996).

    Article  CAS  Google Scholar 

  3. Rubinfeld, B. et al . Stabilization of β-catenin by genetic defects in melanoma cell lines. Science 275, 1790–1792 (1997).

    Article  CAS  Google Scholar 

  4. Morin, P. J. et al . Activation of β-catenin-Tcf signalling in colon cancer by mutations in β-catenin or APC. Science 275, 1787–1790 (1997).

    Article  CAS  Google Scholar 

  5. Korinek, V. et al . Constitutive transcriptional activation by a β-catenin-Tcf complex in APC(−/−) colon carcinoma. Science 275, 1784–1787 (1997).

    Article  CAS  Google Scholar 

  6. Brunner, E., Peter, O., Schweizer, L. & Basler, K. pangolin encodes a Lef-1 homolog that acts downstream of Armadillo to transduce the Wingless signal. Nature 385, 829–833 (1997).

    Article  ADS  CAS  Google Scholar 

  7. Riese, J. et al . LEF-1, a nuclear factor coordinating signalling inputs from wingless and decapentaplegic. Cell 88, 777–787 (1997).

    Article  CAS  Google Scholar 

  8. van de Wetering, M. et al . Armadillo co-activates transcription driven by the product of the Drosophila segment polarity gene dTCF. Cell 88, 789–799 (1997).

    Article  CAS  Google Scholar 

  9. Brannon, M., Gomperts, M., Sumoy, L., Moon, R. T. & Kimelman, D. A. β-catenin/XTcf-3 complex binds to the siamois promoter to regulate dorsal axis specification in Xenopus. Genes Dev. 11, 2359–2370 (1997).

    Article  CAS  Google Scholar 

  10. DiNardo, S., Kuner, J. M., Theis, J. & O'Farrell, P. H. Development of the embryonic pattern in D. melanogaster as revealed by the accumulation of the nuclear engrailed protein. Cell 43, 59–69 (1985).

    Article  CAS  Google Scholar 

  11. DiNardo, S., Sher, E., Heemskerk-Jongens, J., Kassis, J. A. & O'Farrell, P. Two-tiered regulation of spatially patterned engrailed gene expression during Drosophila embryogenesis. Nature 322, 604–609 (1988).

    Article  ADS  Google Scholar 

  12. Martinez Arias, A., Baker, N. & Ingham, P. Role of the segment polarity genes in the definition and maintenance of cell states in the Drosophila embryo. Development 103, 157–170 (1988).

    CAS  Google Scholar 

  13. Bejsovec, A. & Martinez-Arias, A. Roles of wingless in patterning the larval epidermis of Drosophila. Development 113, 471–485 (1991).

    CAS  PubMed  Google Scholar 

  14. Heemskerk, J., DiNardo, S., Kostriken, R. & O'Farrell, P. H. Multiple modes of engrailed regulation in the progression towards cell fate determination. Nature 352, 404–410 (1991).

    Article  ADS  CAS  Google Scholar 

  15. Peifer, M. & Wieschaus, E. The segment polarity gene armadillo encodes a functionally modular protein that is the Drosophila homolog of human plakoglobin. Cell 63, 1167–1178 (1990).

    Article  CAS  Google Scholar 

  16. Von Ohlen, T., Lessing, D., Nusse, R. & Hooper, J. E. Hedgehog signaling regulates transcription through cubitus interruptus, a sequence-specific DNA binding protein. Proc. Natl Acad. Sci. USA 94, 2404–2409 (1997).

    Article  ADS  CAS  Google Scholar 

  17. Hepker, J., Wang, Q. T., Motzny, C. K., Holmgren, R. & Orenic, T. V. Drosophila cubitus interruptus forms a negative feedback loop with patched and regulates expression of Hedgehog target genes. Development 124, 549–558 (1997).

    CAS  PubMed  Google Scholar 

  18. Tiong, S. Y. K. & Nash, D. Genetic analysis of the adenosine3 (Gart) region of the second chromosome in Drosophila melanogaster. Genetics 124, 889–897 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Roose, J. et al . The Xenopus Wnt effector XTcf-3 interacts with Groucho-related transcriptional repressors. Nature 395, 608–612 (1998).

    Article  ADS  CAS  Google Scholar 

  20. Behrens, J. et al . Functional interaction of β-catenin with the transcription factor LEF-1. Nature 382, 638–642 (1996).

    Article  ADS  CAS  Google Scholar 

  21. Paroush, Z. et al . groucho is required for Drosophila neurogenesis, segmentation, and sex determination and interacts directly with Hairy-related bHLH proteins. Cell 79, 805–815 (1994).

    Article  CAS  Google Scholar 

  22. de Celis, J. F. & Ruiz-Gomez, M. groucho and hedgehog regulate engrailed expression in the anterior compartment of the Drosophila wing. Development 121, 3467–3476 (1995).

    CAS  PubMed  Google Scholar 

  23. Noordermeer, J., Johnston, P., Rijsewijk, F., Nusse, R. & Lawrence, P. A. The consequences of ubiquitous expression of the wingless gene in the Drosophila embryo. Development 116, 711–719 (1992).

    CAS  PubMed  Google Scholar 

  24. Bejsovec, A. & Wieschaus, E. Signaling activities of the Drosophila wingless gene are separately mutable and appear to be transduced at the cell surface. Genetics 139, 309–320 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Baker, N. E. Molecular cloning of sequences from wingless, a segment polarity gene in Drosophila: the spatial distribution of a transcript in embryos. EMBO J. 6, 1765–1773 (1987).

    Article  CAS  Google Scholar 

  26. Schrons, H., Knust, E. & Campos-Ortega, J. A. The Enhancer of split complex and adjacent genes in the 96F region of Drosophila melanogaster are required for segregation of neural and epidermal progenitor cells. Genetics 132, 481–503 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by grants from the NIH and the U.S. Army Breast Cancer Research Program (to M.P.), the NSF and the March of Dimes Birth Defects Foundation (to A.B.) and the NWO-GMW (to H.C.).

Author information

Author notes

  1. Robert A. Cavallo, Rachel T. Cox and Melissa M. Moline: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Biology and Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, 27599, North Carolina, USA

    Robert A. Cavallo, Rachel T. Cox, Gordon A. Polevoy & Mark Peifer

  2. Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, 60208, Illinois, USA

    Melissa M. Moline & Amy Bejsovec

  3. Department of Immunology, University Hospital, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands

    Jeroen Roose & Hans Clevers

Authors
  1. Robert A. Cavallo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rachel T. Cox
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Melissa M. Moline
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jeroen Roose
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gordon A. Polevoy
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hans Clevers
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mark Peifer
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Amy Bejsovec
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Amy Bejsovec.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cavallo, R., Cox, R., Moline, M. et al. Drosophila Tcf and Groucho interact to repress Wingless signalling activity. Nature 395, 604–608 (1998). https://doi.org/10.1038/26982

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/26982

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing