Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium
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 vasculature. 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-1lcz, 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-1lcz 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.
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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 [44]
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- Authors
- Fong, G.-H., Rossant, J., Gertsenstein, M., & Breitman, M. L.
- Affiliations
- Mount Sinai Hospital (CA)
- Venue
- Nature
- Published
- 1995-07
- Volume
- 376
- Issue
- 6535
- Pages
- 66-70
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1986559037
- Cited by
- 2,606
- References
- 0
- Citations by year
- 2026: 13 · 2025: 21 · 2024: 28 · 2023: 29 · 2022: 38 · 2021: 36 · 2020: 34 · 2019: 43 · 2018: 52 · 2017: 36 · 2016: 54 · 2015: 62 · 2014: 68 · 2013: 91 · 2012: 94
- FWCI
- 34.32
- 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
- Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
- Keywords
- Flt-1, vascular endothelial growth factor, VEGF receptors, Flk-1, endothelial differentiation, angioblasts, blood islands, cell-matrix interactions, targeted mutations, mouse embryo lethality
- MeSH terms
- Animals, Base Sequence, Cell Differentiation, Embryo, Mammalian, Endothelium, Vascular, Heterozygote, Homozygote, Humans, Lymphokines, Molecular Sequence Data, Proto-Oncogene Proteins, Stem Cells, Endothelial Growth Factors, Mutagenesis, DNA Primers, Receptor Protein-Tyrosine Kinases, Vascular Endothelial Growth Factor Receptor-1, Vascular Endothelial Growth Factors, Vascular Endothelial Growth Factor A, Mice
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