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Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice

Nature volume 376, pages 62–66 (1995)Cite this article

Abstract

THE receptor tyrosine kinase Flk-1 (ref. 1) is believed to play a pivotal role in endothelial development. Expression of the Flk-1 receptor is restricted to endothelial cells and their embryonic precursors2–5, and is complementary to that of its ligand, vascular endothelial growth factor (VEGF)2,3, which is an endothelial-speci-fic mitogen6. Highest levels of flk-1 expression are observed during embryonic vasculogenesis and angiogenesis2–5, and during pathological processes associated with neovascularization, such as tumour angiogenesis7,8. Because flk-1 expression can be detected in presumptive mesodermal yolk-sac blood-island progenitors as early as 7.0 days postcoitum, Flk-1 may mark the putative common embryonic endothelial and haematopoietic precursor, the haemangioblast, and thus may also be involved in early haematopoiesis4. Here we report the generation of mice deficient in Flk-1 by disruption of the gene using homologous recombination in embryonic stem (ES) cells. Embryos homozygous for this mutation die in utero between 8.5 and 9.5 days post-coitum, as a result of an early defect in the development of haematopoietic and endothelial cells. Yolk-sac blood islands were absent at 7.5 days, organized blood vessels could not be observed in the embryo or yolk sac at any stage, and haematopoietic progenitors were severely reduced. These results indicate that Flk-1 is essential for yolk-sac blood-island formation and vasculogenesis in the mouse embryo.

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Author notes

  1. Martin L. Breitman: Deceased

Authors and Affiliations

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

    Fouad Shalaby, Janet Rossant, Terry P. Yamaguchi, Marina Gertsenstein & Martin L. Breitman

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

    Janet Rossant, Terry P. Yamaguchi & Martin L. Breitman

  3. Department of Medicine, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada

    Andre C. Schuh

  4. Institute of Medical Science, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada

    Xiang-Fu Wu & Andre C. Schuh

  5. Division of Haematology/Oncology, The Toronto Hospital, 200 Elizabeth Street, Toronto, Ontario, M5G 2C4, Canada

    Xiang-Fu Wu & Andre C. Schuh

  6. The Canadian Red Cross Society Toronto Blood Centre, 67 College Street, Toronto, Ontario, M5G 2M1, Canada

    Xiang-Fu Wu & Andre C. Schuh

Authors
  1. Fouad Shalaby
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  4. Marina Gertsenstein
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  5. Xiang-Fu Wu
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  6. Martin L. Breitman
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  7. Andre C. Schuh
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Shalaby, F., Rossant, J., Yamaguchi, T. et al. Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice. Nature 376, 62–66 (1995). https://doi.org/10.1038/376062a0

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