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:

ovo/svb integrates Wingless and DER pathways to control epidermis differentiation

Abstract

In Drosophila, as in mammals, epidermal differentiation is controlled by signalling cascades1 that include Wnt proteins2,3 and the ovo/shavenbaby (svb) family of zinc-finger transcription factors4,5,6. Ovo/svb is a complex gene with two genetic functions corresponding to separate control regions: ovo is required for female germline development and svb for epidermal morphogenesis7,8. In the Drosophila embryo, the ventral epidermis consists of the segmental alternance of two major cell types that produce either naked cuticle or cytoplasmic extrusions known as denticles. Wingless signalling specifies smooth cells that produce naked cuticle9, whereas the activation of the Drosophila epidermal growth factor (EGF) receptor (DER) leads to the production of denticles10. Here we show that expression of the ovo/svb gene controls the choice between these cell fates. We find that svb is a key selector gene that, cell autonomously, directs cytoskeletal modifications producing the denticle. The DER pathway promotes denticle formation by activating svb expression. Conversely, Wingless promotes the smooth cell fate through the transcriptional repression of svb bythe bipartite nuclear factor Armadillo/dTcf. Our data indicatethat transcriptional regulation of svb integrates inputs fromthe Wingless and DER pathways and controls epidermal differentiation.

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

Access options

Buy this article

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

Figure 1: svb activity is necessary and sufficient to promote denticle formation.
Figure 2: The Wg pathway represses svb transcription.
Figure 3: The DER signalling pathway directs denticle formation by activating svb expression.
Figure 4: svb transcription integrates the antagonist signals from the Wg and DER pathways.

Similar content being viewed by others

References

  1. Oro, A. E. & Scott, M. P. Splitting hairs: dissecting roles of signaling systems in epidermal development. Cell 95, 575–578 (1998).

    Article  CAS  PubMed  Google Scholar 

  2. Gat, U., DasGupta, R., Degenstein, L. & Fuchs, E. De Novo hair follicle morphogenesis and hair tumors in mice expressing a truncated beta-catenine in skin. Cell 95, 605–614 (1998).

    Article  CAS  PubMed  Google Scholar 

  3. Perrimon, N. The genetic basis of patterned baldness in Drosophila. Cell 76, 781–784 (1994).

    Article  CAS  PubMed  Google Scholar 

  4. Dai, X. et al. The ovo gene required for cuticle formation and oogenesis in flies is involved in hair formation and spermatogenesis in mice. Genes Dev. 12, 3452–3463 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Mevel-Ninio, M., Terracol, R. & Kafatos, F. C. The ovo gene of Drosophila encodes a zinc finger protein required for female germ line development. EMBO J. 10, 2259–2266 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Lu, J., Andrews, J., Pauli, D. & Oliver, B. Drosophila OVO zinc-finger protein regulates ovo and ovarian tumor target promoters. Dev. Genes Evol. 208, 213–222 (1998).

    Article  CAS  PubMed  Google Scholar 

  7. Garfinkel, M. D., Wang, J., Liang, Y. & Mahowald, A. P. Multiple products from the shavenbaby-ovo gene region of Drosophila melanogaster : relationship to genetic complexity. Mol. Cell. Biol. 14, 6809–6818 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Mevel-Ninio, M., Terracol, R., Salles, C., Vincent, A. & Payre, F. ovo, a Drosophila gene required for ovarian development, is specifically expressed in the germline and shares most of its coding sequences with shavenbaby, a gene involved in embryo patterning. Mech. Dev. 49, 83–95 (1995).

    Article  CAS  PubMed  Google Scholar 

  9. 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 

  10. Szuts, D., Freeman, M. & Bienz, M. Antagonism between EGFR and Wingless signalling in the larval cuticle of Drosophila. Development 124, 3209–3219 (1997).

    CAS  PubMed  Google Scholar 

  11. Lawrence, P. A., Sanson, B. & Vincent, J. P. Compartments, wingless and engrailed : patterning the ventral epidermis of Drosophila embryos. Development 122, 4095–4103 (1996).

    CAS  PubMed  Google Scholar 

  12. O'Keefe, L. et al. Spitz and Wingless, emanating from distinct borders, cooperate to establish cell fate across the Engrailed domain in the Drosophila epidermis. Development 124, 4837–4845 (1997).

    CAS  PubMed  Google Scholar 

  13. Dougan, S. & DiNardo, S. Drosophila wingless generates cell type diversity among engrailed expressing cells. Nature 360, 347–350 (1992).

    Article  ADS  CAS  PubMed  Google Scholar 

  14. Brand, A. H. & Perrimon, N. Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development 118, 401–415 (1993).

    CAS  PubMed  Google Scholar 

  15. Mevel-Ninio, M., Fouilloux, E., Guenal, I. & Vincent, A. The three dominant female-sterile mutations of the Drosophila ovo gene are point mutations that create new translation-initiator AUG codons. Development 122, 4131–4138 (1996).

    CAS  PubMed  Google Scholar 

  16. Dickinson, W. J. & Thatcher, J. W. Morphogenesis of denticles and hairs in Drosophila embryos: involvement of actin-associated proteins that also affect adult structures. Cell Motil. Cytoskeleton 38, 9–21 (1997).

    Article  CAS  PubMed  Google Scholar 

  17. Peifer, M., Sweeton, D., Casey, M. & Wieschaus, E. wingless signal and Zeste-white 3 kinase trigger opposing changes in the intracellular distribution of Armadillo. Development 120, 369–380 (1994).

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  19. Barth, A. I., Nathke, I. S. & Nelson, W. J. Cadherins, catenins and APC protein: interplay between cytoskeletal complexes and signaling pathways. Curr. Opin. Cell Biol. 9, 683–690 (1997).

    Article  CAS  PubMed  Google Scholar 

  20. Pai, L. M., Orsulic, S., Bejsovec, A. & Peifer, M. Negative regulation of Armadillo, a Wingless effector in Drosophila. Development 124, 2255–2266 (1997).

    CAS  PubMed  Google Scholar 

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

    Article  ADS  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  24. Yu, X., Riese, J., Eresh, S. & Bienz, M. Transcriptional repression due to high levels of Wingless signalling. EMBO J. 17, 7021–7032 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Sanson, B., White, P. & Vincent, J. P. Uncoupling cadherin-based adhesion from wingless signalling in Drosophila. Nature 383, 627–630 (1996).

    Article  ADS  PubMed  Google Scholar 

  26. Schweitzer, R., Shaharabany, M., Seger, R. & Shilo, B. Z. Secreted Spitz triggers the DER signaling pathway and is a limiting component in embryonic ventral ectoderm determination. Genes Dev. 9, 1518–1529 (1995).

    Article  CAS  PubMed  Google Scholar 

  27. Lee, T., Feig, L. & Montell, D. J. Two distinct roles for Ras is a developmentally regulated cell migration. Development 122, 409–418 (1996).

    CAS  PubMed  Google Scholar 

  28. Schweitzer, R. & Shilo, B. Z. Athousand and one roles for the Drosophila EGF receptor. Trends Genet. 13, 191–196 (1997).

    Article  CAS  PubMed  Google Scholar 

  29. Cadigan, K. M., Fish, M. P., Rulifson, E. J. & Nusse, R. Wingless repression of Drosophila frizzled 2 expression shapes the Wingless morphogen gradient in the wing. Cell 93, 767–777 (1998).

    Article  CAS  PubMed  Google Scholar 

  30. Gabay, L., Seger, R. & Shilo, B. Z. In situ activation pattern of Drosophila EGF receptor pathway during development. Science 277, 1103–1106 (1997).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank M. Freeman, D. Montell, C. Nusslein-Volhard, M. Peifer, B. Shilo, J. P. Vincent, E. Wieschaus, and the Bloomington Stock centre for fly stocks; S. Cohen for providing the Wingless monoclonal antibody; C. Ardourel and M. J. Guinaudy for technical assistance; M. Mével-Ninio, B. Oliver, J. P. Vincent and the members of the lab for stimulating discussions; and B. Oliver, J. P. Vincent and J. Smith for comments on the manuscript. This work was supported by grants from the Centre National de la Recherche Scientifique.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to FranÇois Payre.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Payre, F., Vincent, A. & Carreno, S. ovo/svb integrates Wingless and DER pathways to control epidermis differentiation. Nature 400, 271–275 (1999). https://doi.org/10.1038/22330

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/22330

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

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