VE-cadherin is not required for the formation of nascent blood vessels but acts to prevent their disassembly.
We investigated the role of vascular endothelial (VE)-cadherin in blood vessel morphogenesis and established a temporal correlation linking the failure in vessel morphogenesis in VE-cadherin null embryos to a specific step in vasculogenesis. We showed that the sequence in which blood vessels failed followed the order in which they had formed (ie, those forming first--yolk sac, allantoic and endocardial vessels--were the first to display morphologic abnormalities). We next showed that in place of normal reticulated networks of blood vessels, clusters of platelet endothelial cell adhesion molecule-positive (PECAM+) cells formed within cultured allantois explants from VE-cadherin null embryos. Similarly, a function-blocking VE-cadherin antibody, BV13, caused PECAM+ cell clusters to form in cultured allantois explants from normal mice. Finally, we demonstrated that formation of PECAM+ cell clusters in response to BV13 was not due to a disruption in the formation of nascent vessels but was due to the actual disassembly of nascent vessels. Based on these findings, we conclude that the events of de novo blood vessel formation up to the point at which a vascular epithelium forms (ie, nascent vessels with lumens) are not dependent on VE-cadherin and that VE-cadherin, whose expression is up-regulated following vascular epithelialization, is required to prevent the disassembly of nascent blood vessels.
Crosby
Christopher V
CV
Cardiovascular Developmental Biology Center, Department of Cell Biology, Medical University of South Carolina, 173 Ashley Ave, Charleston, SC 29425, USA.
Fleming
Paul A
PA
Argraves
W Scott
WS
Corada
Monica
M
Zanetta
Lucia
L
Dejana
Elisabetta
E
Drake
Christopher J
CJ
D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D001808:Blood Vessels / Q000196:embryology* / Q000502:physiology*; D015820:Cadherins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D049033:Chorioallantoic Membrane / Q000196:embryology / Q000502:physiology; D004727:Endothelium / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D008648:Mesoderm / Q000502:physiology; D051379:Mice; D018919:Neovascularization, Physiologic / Q000502:physiology*; D009924:Organ Culture Techniques; D015017:Yolk Sac / Q000196:embryology / Q000502:physiology; D000099152:Cadherin 5
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015820:Cadherins; D000099152:Cadherin 5