Cardiovascular failure in mouse embryos deficient in VEGF receptor-3.
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.
Dumont
D J
DJ
Ontario Cancer Institute and Amgen Institute, Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada M5G 2C1.
Jussila
L
L
Taipale
J
J
Lymboussaki
A
A
Mustonen
T
T
Pajusola
K
K
Breitman
M
M
Alitalo
K
K
D000818:Animals; D001808:Blood Vessels / Q000737:chemistry / Q000196:embryology*; D002319:Cardiovascular System / Q000737:chemistry / Q000196:embryology*; D004622:Embryo, Mammalian / Q000098:blood supply / Q000737:chemistry; D005314:Embryonic and Fetal Development; D016228:Endothelial Growth Factors / Q000032:analysis; D004730:Endothelium, Vascular / Q000737:chemistry / Q000196:embryology*; D018390:Gene Targeting; D006410:Hematopoiesis; D006579:Heterozygote; D006720:Homozygote; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008024:Ligands; D051379:Mice; D018919:Neovascularization, Physiologic; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D042582:Vascular Endothelial Growth Factor C; D040321:Vascular Endothelial Growth Factor Receptor-3
D016228:Endothelial Growth Factors; D008024:Ligands; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011956:Receptors, Cell Surface; D042582:Vascular Endothelial Growth Factor C; D020794:Receptor Protein-Tyrosine Kinases; D040321:Vascular Endothelial Growth Factor Receptor-3