Abstract
Vascular endothelial growth factor (VEGF) is a key regulator of blood vessel development in embryos and angiogenesis in adult tissues. Unlike VEGF, the related VEGF-C stimulates the growth of lymphatic vessels through its specific lymphatic endothelial receptor VEGFR-3. Here it is shown that targeted inactivation of the gene encoding VEGFR-3 resulted in defective blood vessel development in early mouse embryos. Vasculogenesis and angiogenesis occurred, but large vessels became abnormally organized with defective lumens, leading to fluid accumulation in the pericardial cavity and cardiovascular failure at embryonic day 9.5. Thus, VEGFR-3 has an essential role in the development of the embryonic cardiovascular system before the emergence of the lymphatic vessels.
Publication types
- Research Support, Non-U.S. Gov't
MeSH terms
- Animals
- Blood Vessels / chemistry
- Blood Vessels / embryology*
- Cardiovascular System / chemistry
- Cardiovascular System / embryology*
- Embryo, Mammalian / blood supply
- Embryo, Mammalian / chemistry
- Embryonic and Fetal Development
- Endothelial Growth Factors / analysis
- Endothelium, Vascular / chemistry
- Endothelium, Vascular / embryology*
- Gene Targeting
- Hematopoiesis
- Heterozygote
- Homozygote
- Immunohistochemistry
- In Situ Hybridization
- Ligands
- Mice
- Neovascularization, Physiologic
- Platelet Endothelial Cell Adhesion Molecule-1 / analysis
- Receptor Protein-Tyrosine Kinases / analysis
- Receptor Protein-Tyrosine Kinases / genetics
- Receptor Protein-Tyrosine Kinases / physiology*
- Receptors, Cell Surface / analysis
- Receptors, Cell Surface / genetics
- Receptors, Cell Surface / physiology*
- Signal Transduction
- Vascular Endothelial Growth Factor C
- Vascular Endothelial Growth Factor Receptor-3
Substances
- Endothelial Growth Factors
- Ligands
- Platelet Endothelial Cell Adhesion Molecule-1
- Receptors, Cell Surface
- Vascular Endothelial Growth Factor C
- Receptor Protein-Tyrosine Kinases
- Vascular Endothelial Growth Factor Receptor-3