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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Base Sequence
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Cell Differentiation
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DNA Primers
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Embryo, Mammalian / blood supply
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Endothelial Growth Factors / physiology
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Endothelium, Vascular / cytology
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Endothelium, Vascular / embryology*
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Heterozygote
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Homozygote
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Humans
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Lymphokines / physiology
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Mice
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Molecular Sequence Data
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Mutagenesis
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / physiology*
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Receptor Protein-Tyrosine Kinases / genetics
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Receptor Protein-Tyrosine Kinases / physiology*
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Stem Cells
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factor Receptor-1
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Vascular Endothelial Growth Factors
Substances
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DNA Primers
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Endothelial Growth Factors
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Lymphokines
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Proto-Oncogene Proteins
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
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Receptor Protein-Tyrosine Kinases
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Vascular Endothelial Growth Factor Receptor-1