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:

Placental defect and embryonic lethality in mice lacking hepatocyte growth factor/scatter factor

Nature volume 373, pages 702–705 (1995)Cite this article

Abstract

HEPATOCYTE growth factor/scatter factor (HGF/SF) functions as a mitogen, motogen and morphogen for a variety of cultured cells1–7. The genes for HGF/SF and its receptor (the c-met protooncogene product8) are expressed in many tissues during the embryonic periods and in the adult9–14. HGF/SF is thought to mediate a signal exchange between the mesenchyme and epithelia during mouse development15. To examine the physiological role of HGF/SF, we generated mutant mice with a targeted disruption of the HGF/SF gene. Here we report that homozygous mutant embryos have severely impaired placentas with markedly reduced numbers of labyrinthine trophoblast cells, and die before birth. The growth of trophoblast cells was stimulated by HGF/SF in vitro, and the HGF/SF activity was released by allantois in primary culture of normal but not mutant embryos. These findings suggest that HGF/SF is an essential mediator of allantoic mesenchyme-trophoblastic epithelia interaction required for placental organogenesis.

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. Gohda, E. et al. J. clin. Invest. 81, 414–419 (1988).

    Article  CAS  Google Scholar 

  2. Zarnegar, R. & Michalopoulos, G. Cancer Res. 49, 3314–3320 (1989).

    CAS  PubMed  Google Scholar 

  3. Nakamura, T. et al. Nature 342, 440–443 (1989).

    Article  ADS  CAS  Google Scholar 

  4. Rubin, J. S. et al. Proc. natn. Acad. Sci. U.S.A. 88, 415–419 (1991).

    Article  ADS  CAS  Google Scholar 

  5. Stoker, M., Gherardi, E., Perryman, M. & Gray, J. Nature 327, 239–242 (1987).

    Article  ADS  CAS  Google Scholar 

  6. Weidner, K. M. et al. Proc. natn. Acad. Sci. U.S.A. 88, 7001–7005 (1991).

    Article  ADS  CAS  Google Scholar 

  7. Montesano, R., Matsumoto, K., Nakamura, T. & Orci, L. Cell 67, 901–908 (1991).

    Article  CAS  Google Scholar 

  8. Bottaro, D. P. et al. Science 251, 802–804 (1991).

    Article  ADS  CAS  Google Scholar 

  9. Miyazawa, K. et al. Biochem. biophys. Res. Commun. 163, 967–973 (1989).

    Article  CAS  Google Scholar 

  10. Tashiro, K. et al. Proc. natn. Acad. Sci. U.S.A. 87, 3200–3204 (1990).

    Article  ADS  CAS  Google Scholar 

  11. Defrances, M. C., Wolf, H. K., Michalopoulos, G. K. & Zarnegar, R. Development 116, 387–395 (1992).

    CAS  PubMed  Google Scholar 

  12. Chan, A. M.-L. et al. Oncogene 2, 593–599 (1988).

    CAS  PubMed  Google Scholar 

  13. Iyer, A. et al. Cell Growth Differ. 1, 87–95 (1990).

    CAS  PubMed  Google Scholar 

  14. Di Renzo, M. F. et al. Oncogene 6, 1997–2003 (1991).

    CAS  PubMed  Google Scholar 

  15. Sonnenberg, E., Meyer, D., Weidner, K. M. & Birchmeier, C. J. Cell Biol. 123, 223–235 (1993).

    Article  CAS  Google Scholar 

  16. Okigaki, M., Komada, M., Uehara, Y., Miyazawa, K. & Kitamura, N. Biochemistry 31, 9555–9561 (1992).

    Article  CAS  Google Scholar 

  17. Schmidt, C. et al. Nature 373, 699–702 (1995).

    Article  ADS  CAS  Google Scholar 

  18. Muntener, M. & Hsu, Y.-C. Acta anat. 98, 241–252 (1977).

    Article  CAS  Google Scholar 

  19. Garbis-Berkvens, J. M. & Peters, P. W. J. in Pharmacokinetics in Teratogenesis: I (eds Nau, H. & Scott, W. J. J.) 13–44 (CRC, Boca Raton, 1987).

    Google Scholar 

  20. Peel, S. & Bulmer, D. J. Anat. 124, 675–687 (1977).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Rossant, J. & Tamura-Lis, W. J. Embryol. exp. Morph. 62, 217–227 (1981).

    CAS  PubMed  Google Scholar 

  22. Barlow, P. W. & Sherman, M. I. J. Embryol. exp. Morphol. 27, 447–465 (1972).

    CAS  PubMed  Google Scholar 

  23. Bussolino, F. et al. J. Cell Biol. 119, 629–641 (1992).

    Article  CAS  Google Scholar 

  24. Grant, D. S. et al. Proc. natn. Acad. Sci. U.S.A. 90, 1937–1941 (1993).

    Article  ADS  CAS  Google Scholar 

  25. Rudnicki, M. A., Braun, T., Hinuma, S. & Jaenisch, R. Cell 71, 383–390 (1992).

    Article  CAS  Google Scholar 

  26. Okajima, A., Miyazawa, K. & Kitamura, N. Eur. J. Biochem. 193, 375–381 (1990).

    Article  CAS  Google Scholar 

  27. Li, E., Bestor, T. H. & Jaenisch, R. Cell 69, 915–926 (1992).

    Article  CAS  Google Scholar 

  28. Takeshima, H. et al. Nature 369, 556–559 (1994).

    Article  ADS  CAS  Google Scholar 

  29. Bradley, A. in Teratocarcinomas and Embryonic Stem Cells: A Practical Approach (eds Robertson, E. J.) 113–151 (IRL, Oxford, 1987).

    Google Scholar 

  30. Uehara, Y. & Kitamura, N. J. Cell Biol. 117, 889–894 (1992).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute for Liver Research, Kansai Medical University, Moriguchi, Osaka, 570, Japan

    Yoshihiko Uehara & Naomi Kitamura

  2. Department of Cell Biology, Cancer Institute, Tokyo, 170, Japan

    Yoshihiko Uehara, Osamu Minowa, Junko Kuno & Tetsuo Noda

  3. Department of Anatomy, Kyoto University, School of Medicine, Kyoto, 606, Japan

    Chisato Mori & Kohei Shiota

Authors
  1. Yoshihiko Uehara
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Osamu Minowa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chisato Mori
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kohei Shiota
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Junko Kuno
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tetsuo Noda
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Naomi Kitamura
    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

Uehara, Y., Minowa, O., Mori, C. et al. Placental defect and embryonic lethality in mice lacking hepatocyte growth factor/scatter factor. Nature 373, 702–705 (1995). https://doi.org/10.1038/373702a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/373702a0

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