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:

FGF-4 and BMP-2 have opposite effects on limb growth

Nature volume 361, pages 68–71 (1993)Cite this article

Abstract

LIMB development is dependent on epithelial–mesenchymal interactions. The apical ectodermal ridge (AER), a specialized epithelium at the limb tip, stimulates proliferation of underlying mesenchyme, causing directed limb outgrowth1 (for review see ref. 2). Several genes are expressed in the mouse AER3–10, including Fgf-4 (fibroblast growth factor-4)11,12 and Bmp-2 (bone mor-phogenetic protein-2)13, both of which encode secreted signalling molecules. Using a culture system developed to explore the function of molecules produced by the AER, we have shown that FGF-4 protein stimulates proliferation of mesenchyme in the early mouse limb-bud. This suggests that FGF-4 serves that major function of the AER. In contrast, BMP-2 inhibits limb growth, suggesting that as a result the AER may serve a hitherto unrecognized inhibitory function. Furthermore, the extent of limb outgrowth can be modulated by mixing the two signalling molecules, suggesting that limb growth is regulated by a combination of stimulatory and inhibitory signals from the AER.

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. Saunders, J. W. Jr. J. exp. Zool. 108, 363–403 (1948).

    Article  Google Scholar 

  2. Tabin, C. J. Cell 66, 199–217 (1991).

    Article  CAS  Google Scholar 

  3. Dollé, P. et al. Nature 342, 702–705 (1989).

    Article  ADS  Google Scholar 

  4. Hill, R. E. et al. Genes Dev. 3, 26–37 (1989).

    Article  CAS  Google Scholar 

  5. Robert, B., Sassoon, D., Jacq, B., Gehring, W. & Buckingham, M. EMBO J. 8, 91–100 (1989).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  7. Davis, C. A., Holmyard, D. P., Millen, K. J. & Joyner, A. L. Development 111, 287–298 (1991).

    CAS  PubMed  Google Scholar 

  8. Jones, C. M., Lyons, K. M. & Hogan, B. L. M. Development 111, 531–542 (1991).

    CAS  PubMed  Google Scholar 

  9. Jackson-Grusby, L., Kuo, A. & Leder, P. Genes Dev. 6, 29–37 (1992).

    Article  CAS  Google Scholar 

  10. Ruberte, E., Friederich, V., Morriss-Kay, G. & Chambon, P. Development 115, 973–987 (1992).

    CAS  PubMed  Google Scholar 

  11. Niswander, L. & Martin, G. R. Development 114, 755–768 (1992).

    CAS  PubMed  Google Scholar 

  12. Suzuki, H. R. et al. Devl Biol. 150, 219–222 (1992).

    Article  CAS  Google Scholar 

  13. Lyons, K. M., Pelton, R. W. & Hogan, B. L. M. Development 109, 833–844 (1990).

    CAS  PubMed  Google Scholar 

  14. Summerbell, D. J. Embryol. exp. Morph. 32, 651–660 (1974).

    CAS  Google Scholar 

  15. Delli-Bovi, P. et al. Molec. cell. Biol. 8, 2933–2941 (1988).

    Article  CAS  Google Scholar 

  16. Dionne, C. A. et al. EMBO J. 9, 2685–2692 (1990).

    Article  CAS  Google Scholar 

  17. Mansukhani, A., Moscatelli, D., Talarico, D., Levytska, V. & Basilico, C. Proc. natn. Acad. Sci. U.S.A. 87, 4378–4382 (1990).

    Article  ADS  CAS  Google Scholar 

  18. Orr-Urtreger, A., Givol, D., Yayon, A., Yarden, Y. & Lonai, P. Development 113, 1419–1434 (1991).

    CAS  PubMed  Google Scholar 

  19. Peters, K. G., Werner, S. & Williams, L. T. Development 114, 233–243 (1992).

    CAS  PubMed  Google Scholar 

  20. Morgan, B. A., Izpisua-Belmonte, J.-C., Duboule, D. & Tabin, C. J. Nature 358, 236–239 (1992).

    Article  ADS  CAS  Google Scholar 

  21. Dollė, P., Izpisu̇a-Belmonte, J.-C., Falkenstein, H., Renucci, A. & Duboule, D. Nature 342, 767–772 (1989).

    Article  ADS  Google Scholar 

  22. Takuwa, Y., Ohse, C., Wang, E. A., Wozney, J. M. & Yamashita, K. Biochem. biophys. Res. Commun. 174, 96–101 (1991).

    Article  CAS  Google Scholar 

  23. Wilkinson, D. G., Bhatt, S. & McMahon, A. P. Development 105, 131–136 (1989).

    CAS  Google Scholar 

  24. Haub, O. & Goldfarb, M. Development 112, 397–406 (1991).

    CAS  PubMed  Google Scholar 

  25. Smith, D. B. & Johnson, K. S. Gene 67, 31–40 (1988).

    Article  CAS  Google Scholar 

  26. Hebert, J. M., Basilico, C., Goldfarb, M., Haub, O. & Martin, G. R. Devl Biol. 138, 454–463 (1990).

    Article  CAS  Google Scholar 

  27. Wanek, N., Muneoka, K., Holler-Dinsmore, G., Burton, R. & Bryant, S. V. J. exp. Zool. 249, 41–49 (1989).

    Article  CAS  Google Scholar 

  28. Neubert, D. & Barrach, H.-J. in Methods in Prenatal Toxicology (eds Neubert, D., Merker. H.-J. & Kwasigroch, T. E.) 241–251 (Georg Thieme, Stuttgart, 1977).

    Google Scholar 

  29. Frohman, M. A., Boyle, M. & Martin, G. R. Development 110, 589–607 (1990).

    CAS  Google Scholar 

  30. Dollé, P., Izpisùa-Belmonte, J.-C., Boncinelli, E. & Duboule, D. Mech. Dev. 36, 3–13 (1991).

    Article  Google Scholar 

  31. Aono, H. & Ide, H. Devl Biol. 128, 136–141 (1988).

    Article  CAS  Google Scholar 

  32. Hinchliffe, J. R. & Johnson, D. R. The Development of the Vertebrate Limb: An Approach through Experiment, Genetics and Evolution (Clarendon, Oxford, 1980).

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Anatomy and Program in Developmental Biology, School of Medicine, University of California, San Francisco, California, 94143, USA

    Lee Niswander & Gail R. Martin

Authors
  1. Lee Niswander
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gail R. Martin
    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

Niswander, L., Martin, G. FGF-4 and BMP-2 have opposite effects on limb growth. Nature 361, 68–71 (1993). https://doi.org/10.1038/361068a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/361068a0

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