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:

Epithelial transformation of metanephric mesenchyme in the developing kidney regulated by Wnt-4

Nature volume 372, pages 679–683 (1994)Cite this article

Abstract

THE kidney has been widely exploited as a model system for the study of tissue inductions regulating vertebrate organogenesis1,2. Kidney development is initiated by the ingrowth of the Wolfian duct-derived ureteric bud into the presumptive kidney mesenchyme. In response to a signal from the ureter, mesenchymal cells condense, aggregate into pretubular clusters and undergo an epithelial conversion generating a simple tubule. This then undergoes morphogenesis and is transformed into the excretory system of the kidney, the nephron. We report here that the expression of Wnt-4, which encodes a secreted glycoprotein, correlates with, and is required for, kidney tubulogenesis. Mice lacking Wnt-4 activity fail to form pretubular cell aggregates; however, other aspects of mesenchymal and ureteric development are unaffected. Thus, Wnt-4 appears to act as an autoinducer of the mesenchyme to epithelial transition that underlies nephron development.

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

Similar content being viewed by others

References

  1. Grobstein, C. J. exp. Zool. 130, 319–340 (1955).

    Article  Google Scholar 

  2. Saxén, L. Organogenesis of the Kidney (Cambridge Univ. Press, 1987).

    Book  Google Scholar 

  3. Parr, B. et al. Development 119, 247–268 (1993).

    CAS  Google Scholar 

  4. Pritchard-Jones, K. et al. Nature 346, 194–197 (1990).

    Article  ADS  CAS  Google Scholar 

  5. Armstrong, J. F. et al. Mech. Dev. 40, 85–97 (1993).

    Article  CAS  Google Scholar 

  6. Mugrauer, G. & Ekblom, P. J. Cell Biol. 112, 13–25 (1991).

    Article  CAS  Google Scholar 

  7. Dressier, G. R. et al. Development 109, 787–795 (1990).

    Google Scholar 

  8. Rothenpieler, U. W. & Dressier, G. R. Development 119, 711–720 (1993).

    CAS  PubMed  Google Scholar 

  9. Plachov, D. et al. Development 110, 643–651 (1990).

    CAS  PubMed  Google Scholar 

  10. Pachnis, V., Mankoo, B. & Constantini, F. Development 119, 1005–1017 (1993).

    CAS  Google Scholar 

  11. Schuchardt, A. et al. Nature 367, 380–383 (1994).

    Article  ADS  CAS  Google Scholar 

  12. Sonnenberg, E. et al. EMBO J. 10, 3693–3702 (1991).

    Article  CAS  Google Scholar 

  13. Tessarollo, L. et al. Development 115, 11–20 (1992).

    CAS  PubMed  Google Scholar 

  14. Saxén, L. & Saksela, E. Expl Cell Res. 66, 369–377 (1971).

    Article  Google Scholar 

  15. Moon, R. T. et al. Development 119, 97–111 (1993).

    CAS  PubMed  Google Scholar 

  16. McCrea, P. D., Turck, C. W. & Gumbiner, B. Science 254, 1359–1361 (1991).

    Article  ADS  CAS  Google Scholar 

  17. Gumbiner, B. M. & McCrea, P. D. J. Cell Sci. 17 (suppl.), 155–158 (1993).

    Article  CAS  Google Scholar 

  18. Noordermeer, J., Klingensmith, J., Perrimon, N. & Nusse, R. Nature 367, 80–83 (1994).

    Article  ADS  CAS  Google Scholar 

  19. Siegfried, E., Wilder, E. L. & Perrimon, N. Nature 367, 76–80 (1994).

    Article  ADS  CAS  Google Scholar 

  20. Bradley, R. S., Cowin, P. & Brown, A. M. J. Cell Biol. 123, 1857–1865 (1993).

    Article  CAS  Google Scholar 

  21. Hinck, L., Nelson, W. J. & Papkoff, J. J. Cell Biol. 124, 729–741 (1994).

    Article  CAS  Google Scholar 

  22. Shimamura, K., Hirano, S., McMahon, A. P. & Takeichi, M. Development 120, 2225–2234 (1994).

    CAS  PubMed  Google Scholar 

  23. Vestweber, D., Kemler, R. & Ekblom, P. Devi Biol. 112, 213–221 (1985).

    Article  CAS  Google Scholar 

  24. Wilkinson, D. G., Bailes, J. A., Champion, J. E. & McMahon, A. P. Development 99, 493–500 (1987).

    CAS  PubMed  Google Scholar 

  25. Gavin, B., McMahon, J. A. & McMahon, A. P. Genes Dev. 4, 2319–2332 (1990).

    Article  CAS  Google Scholar 

  26. Swiatek, P. J. et al. Genes Dev. 8, 707–719 (1994).

    Article  CAS  Google Scholar 

  27. Soriano, P., Montgomery, C., Geske, R. & Bradley, A. Cell 64, 693–702 (1991).

    Article  CAS  Google Scholar 

  28. Mansour, S. L., Thomas, K. R. & Capecchi, M. R. Nature 336, 348–352 (1988).

    Article  ADS  CAS  Google Scholar 

  29. McMahon, A. P. & Bradley, A. Cell 62, 1073–1085 (1990).

    Article  CAS  Google Scholar 

  30. Stanton, B. R. et al. Genes Dev. 6, 2235–2247 (1992).

    Article  CAS  Google Scholar 

Download references

Author information

Author notes

  1. Kevin Stark

    Present address: Amgen Inc., 1840 DeHavilland Drive, Thousand Oaks, California, 91320, USA

  2. Galya Vassileva

    Present address: Roche Institute for Molecular Biology, Roche Research Center, 340 Kingsland Street, Nutley, New Jersey, 07710, USA

Authors and Affiliations

  1. Department of Molecular and Cellular Biology, The Biolabs, Harvard University, 16 Divinity Avenue, Cambridge, Massachusetts, 02138, USA

    Kevin Stark, Seppo Vainio, Galya Vassileva & Andrew P. McMahon

Authors
  1. Kevin Stark
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Seppo Vainio
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Galya Vassileva
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Andrew P. McMahon
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Stark, K., Vainio, S., Vassileva, G. et al. Epithelial transformation of metanephric mesenchyme in the developing kidney regulated by Wnt-4. Nature 372, 679–683 (1994). https://doi.org/10.1038/372679a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/372679a0

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