Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice
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 precursors, and is complementary to that of its ligand, vascular endothelial growth factor (VEGF), which is an endothelial-specific mitogen. Highest levels of flk-1 expression are observed during embryonic vasculogenesis and angiogenesis, and during pathological processes associated with neovascularization, such as tumour angiogenesis. 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 haematopoiesis. 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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VEGF-/- and VEGF+/- mice were embryonic lethal or associated with profound defects in vasculogenesis and developmental angiogenesis.
“This was an important distinction since in other knockout models e.g. VEGF-/- and +/- mice were embryonic lethal or associated with profound defects in vasculogenesis and developmental angiogenesis [44], [45].”
From Rac2 Controls Tumor Growth, Metastasis and M1-M2 Macrophage Differentiation In Vivo (2014) · cites this paper as [45]
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- Authors
- Shalaby, F., Rossant, J., Yamaguchi, T. P., Gertsenstein, M., Wu, X.-F., Breitman, M. L., & Schuh, A. C.
- Affiliations
- Mount Sinai Hospital (CA)
- University of Toronto (CA)
- Venue
- Nature
- Published
- 1995-07
- Volume
- 376
- Issue
- 6535
- Pages
- 62-66
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2046516822
- Cited by
- 3,931
- References
- 1
- Citations by year
- 2026: 22 · 2025: 38 · 2024: 41 · 2023: 50 · 2022: 64 · 2021: 62 · 2020: 59 · 2019: 74 · 2018: 86 · 2017: 82 · 2016: 106 · 2015: 104 · 2014: 126 · 2013: 132 · 2012: 158
- FWCI
- 42.55
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Zebrafish Biomedical Research Applications
- Keywords
- Flk-1, vascular endothelial growth factor receptor, vasculogenesis, yolk sac, hematopoiesis, endothelial development, knockout mice, embryonic lethality, angiogenesis
- MeSH terms
- Animals, Base Sequence, Blood Vessels, Cell Line, Genes, Lethal, Genetic Vectors, Hematopoiesis, Lac Operon, Molecular Sequence Data, Stem Cells, Yolk Sac, Restriction Mapping, Mutagenesis, DNA Primers, Receptors, Growth Factor, Receptor Protein-Tyrosine Kinases, Receptors, Vascular Endothelial Growth Factor, Mice
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