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.

Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium

Nature volume 376, pages 66–70 (1995)Cite this article

Abstract

THE vascular endothelial growth factor (VEGF) and its high-affinity binding receptors, the tyrosine kinases Flt-1 and Flk-1, are thought to be important for the development of embryonic vasculature1–8. Here we report that Flt-1 is essential for the organization of embryonic vasculature, but is not essential for endothelial cell differentiation. Mouse embryos homozygous for a targeted mutation in the flt-1 locus, flt-llcz formed endothelial cells in both embryonic and extra-embryonic regions, but assembled these cells into abnormal vascular channels and died in utero at mid-somite stages. At earlier stages, the blood islands of flt-llcz homozygotes were abnormal, with angioblasts in the interior as well as on the periphery. We suggest that the Flt-1 signalling pathway may regulate normal endothelial cell-cell or cell-matrix interactions during vascular development.

This is a preview of subscription content

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

Buy

All prices are NET prices.

References

  1. De Vries, C. et al. Science 255, 989–991 (1992).

    ADS  CAS  Article  Google Scholar 

  2. Millauer, B., Shawver, L. K., Plate, K. H., Risau, W. & Ullrich, A. Nature 367, 576–579 (1994).

    ADS  CAS  Article  Google Scholar 

  3. Millauer, B. et al. Cell 72, 835–846 (1993).

    CAS  Article  Google Scholar 

  4. Breier, G., Albrecht, U., Sterrer, S. & Risau, W. Development 114, 521–534 (1992).

    CAS  Google Scholar 

  5. Peters, K. G., De Vries, C. & William, L. T. Proc. natn. Acad. Sci. U.S.A. 90, 8915–8919 (1993).

    ADS  CAS  Article  Google Scholar 

  6. Yamaguchi, T. P., Dumont, D. J., Colon, R. A., Breitman, M. L. & Rossant, J. Development 118, 489–498 (1993).

    CAS  PubMed  Google Scholar 

  7. Leung, D. W., Cachianes, G., Kuang, W.-J., Goeddel, D. V. & Ferrara, N. Science 246, 1306–1309 (1989).

    ADS  CAS  Article  Google Scholar 

  8. Shibuya, M. et al. Oncogene 5, 519–524 (1990).

    CAS  Google Scholar 

  9. Mansour, S. L., Goddard, J. M. & Capecchi, M. R. Development 117, 13–28 (1993).

    CAS  Google Scholar 

  10. Nagy, A., Rossant, J., Nagy, R., Abramow-Newerly, W. & Roder, J. C. Proc. natn. Acad. Sci. U.S.A. 90, 8424–8428 (1993).

    ADS  CAS  Article  Google Scholar 

  11. Baldwin, H. S. et al. Development 120, 2539–2553 (1994).

    CAS  PubMed  Google Scholar 

  12. Finnerty, H. et al. Oncogene 8, 2293–2298 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Kaipainen, A. et al. Proc. natn. Acad. Sci. U.S.A. 92, 3566–3570 (1995).

    ADS  CAS  Article  Google Scholar 

  14. Pajusola, K. et al. Cancer Res. 52, 5738–5743 (1992).

    CAS  PubMed  Google Scholar 

  15. Partanen, J. et al. Molec. cell. Biol. 12, 1698–1707 (1992).

    CAS  Article  Google Scholar 

  16. Korhonen, J., Polvi, A., Partenen, J. & Alitalo, K. Oncogene 9, 395–403 (1994).

    CAS  PubMed  Google Scholar 

  17. Dumont, D. J., Gradwohl, G. J., Fong, G.-H., Auerbach, R. & Breitman, M. L. Oncogene 8, 1293–1301 (1993).

    CAS  PubMed  Google Scholar 

  18. Noden, D. M. Am. Rev. resp. Dis. 149, 1097–1103 (1989).

    Article  Google Scholar 

  19. Risau, W. et al. Development 102, 471–478 (1988).

    CAS  PubMed  Google Scholar 

  20. Risau, W. in The Development of the Vascular System (eds Feinberg, R. N., Sherer, G. K. & Auerbach, R.) 58–68 (Karger, Basel, 1991).

    Google Scholar 

  21. Patan, S., Haenni, B. & Burri, P. H. Anat. Embryol. 187, 121–130 (1993).

    CAS  Article  Google Scholar 

  22. Shalaby, F. et al. Nature 376, 62–66 (1995).

    ADS  CAS  Article  Google Scholar 

  23. Seetharam, L. et al. Oncogene 10, 135–147 (1995).

    CAS  PubMed  Google Scholar 

  24. Park, J. E., Chen, H. H., Winer, J., Houck, K. A. & Ferrara, N. J. biol. Chem. 269, 25646–25654 (1994).

    CAS  PubMed  Google Scholar 

  25. Dumont, D. J. et al. Genes Dev. 8, 1897–1909 (1994).

    CAS  Article  Google Scholar 

  26. Iwama, A. et al. Biochem. biophys. Res. Commun. 195, 301–309 (1993).

    CAS  Article  Google Scholar 

  27. Hogan, B., Beddington, R., Constantini, F. & Lacy, E. Manipulating the Mouse Embryo, 2nd edn (Cold Spring Harbor Laboratory Press, NY, 1994).

    Google Scholar 

Download references

Author information

Author notes

  1. Guo-Hua Fong

    Present address: The Lawson Research Institute, St Joseph's Health Centre, 268 Grosvenor Street, London, Ontario, N6A 4V2, Canada

  2. Martin L. Breitman: Deceased

Affiliations

  1. Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario, M5G 1X5, Canada

    Guo-Hua Fong, Janet Rossant, Marina Gertsenstein & Martin L. Breitman

  2. Department of Molecular and Medical Genetics, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada

    Janet Rossant & Martin L. Breitman

Authors
  1. Guo-Hua Fong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Janet Rossant
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marina Gertsenstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Martin L. Breitman
    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

Fong, GH., Rossant, J., Gertsenstein, M. et al. Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium. Nature 376, 66–70 (1995). https://doi.org/10.1038/376066a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/376066a0

Further reading

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