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


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1995-07

AUTHORS

Fouad Shalaby, Janet Rossant, Terry P. Yamaguchi, Marina Gertsenstein, Xiang-Fu Wu, Martin L. Breitman, Andre C. Schuh

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. More... »

PAGES

62-66

Journal

TITLE

Nature

ISSUE

6535

VOLUME

376

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/376062a0

    DOI

    http://dx.doi.org/10.1038/376062a0

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1021421211

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/7596435


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    29 schema:description 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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