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 via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
De Vries, C. et al. Science 255, 989–991 (1992).
Millauer, B., Shawver, L. K., Plate, K. H., Risau, W. & Ullrich, A. Nature 367, 576–579 (1994).
Millauer, B. et al. Cell 72, 835–846 (1993).
Breier, G., Albrecht, U., Sterrer, S. & Risau, W. Development 114, 521–534 (1992).
Peters, K. G., De Vries, C. & William, L. T. Proc. natn. Acad. Sci. U.S.A. 90, 8915–8919 (1993).
Yamaguchi, T. P., Dumont, D. J., Colon, R. A., Breitman, M. L. & Rossant, J. Development 118, 489–498 (1993).
Leung, D. W., Cachianes, G., Kuang, W.-J., Goeddel, D. V. & Ferrara, N. Science 246, 1306–1309 (1989).
Shibuya, M. et al. Oncogene 5, 519–524 (1990).
Mansour, S. L., Goddard, J. M. & Capecchi, M. R. Development 117, 13–28 (1993).
Nagy, A., Rossant, J., Nagy, R., Abramow-Newerly, W. & Roder, J. C. Proc. natn. Acad. Sci. U.S.A. 90, 8424–8428 (1993).
Baldwin, H. S. et al. Development 120, 2539–2553 (1994).
Finnerty, H. et al. Oncogene 8, 2293–2298 (1993).
Kaipainen, A. et al. Proc. natn. Acad. Sci. U.S.A. 92, 3566–3570 (1995).
Pajusola, K. et al. Cancer Res. 52, 5738–5743 (1992).
Partanen, J. et al. Molec. cell. Biol. 12, 1698–1707 (1992).
Korhonen, J., Polvi, A., Partenen, J. & Alitalo, K. Oncogene 9, 395–403 (1994).
Dumont, D. J., Gradwohl, G. J., Fong, G.-H., Auerbach, R. & Breitman, M. L. Oncogene 8, 1293–1301 (1993).
Noden, D. M. Am. Rev. resp. Dis. 149, 1097–1103 (1989).
Risau, W. et al. Development 102, 471–478 (1988).
Risau, W. in The Development of the Vascular System (eds Feinberg, R. N., Sherer, G. K. & Auerbach, R.) 58–68 (Karger, Basel, 1991).
Patan, S., Haenni, B. & Burri, P. H. Anat. Embryol. 187, 121–130 (1993).
Shalaby, F. et al. Nature 376, 62–66 (1995).
Seetharam, L. et al. Oncogene 10, 135–147 (1995).
Park, J. E., Chen, H. H., Winer, J., Houck, K. A. & Ferrara, N. J. biol. Chem. 269, 25646–25654 (1994).
Dumont, D. J. et al. Genes Dev. 8, 1897–1909 (1994).
Iwama, A. et al. Biochem. biophys. Res. Commun. 195, 301–309 (1993).
Hogan, B., Beddington, R., Constantini, F. & Lacy, E. Manipulating the Mouse Embryo, 2nd edn (Cold Spring Harbor Laboratory Press, NY, 1994).
Author information
Authors and Affiliations
Rights 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
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/376066a0
This article is cited by
-
Obesity and prostate cancer — microenvironmental roles of adipose tissue
Nature Reviews Urology (2023)
-
Regulation of brain endothelial cell physiology by the TAM receptor tyrosine kinase Mer
Communications Biology (2023)
-
Biology and therapeutic targeting of vascular endothelial growth factor A
Nature Reviews Molecular Cell Biology (2023)
-
Genetic polymorphisms in VEGFA and VEGFR2 genes associated with coronary heart disease susceptibility and severity
Molecular Biology Reports (2023)
-
A defined clathrin-mediated trafficking pathway regulates sFLT1/VEGFR1 secretion from endothelial cells
Angiogenesis (2023)
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.
