VEGF signaling is required for the assembly but not the maintenance of embryonic blood vessels.
Here we investigated the importance of vascular endothelial growth factor (VEGF) signaling to the de novo formation of embryonic blood vessels, vasculogenesis, as opposed to the maintenance of blood vessels. We found that antagonizing the activity of the VEGF signaling pathway by using soluble VEGF receptor 1 (sFlt1) or VEGF antibodies inhibited vasculogenesis that occurs in embryos and in cultures of 7.5 days postcoitus prevascular mesoderm. Antagonist treatment resulted in the formation of clusters of endothelial cells not normally observed during vasculogenesis. In contrast, when embryos with established vasculatures or cultures of vascularized mesoderm were treated with sFlt1 or VEGF antibodies, no discernible alterations to the preexisting blood vessels were observed. These observations indicate that, although VEGF signaling is required to promote the mesenchymal to epithelial transition by which angioblasts assemble into nascent endothelial tubes, it is not required by endothelial cells to maintain their organization as an endothelium.
Argraves
W Scott
WS
Cardiovascular Developmental Biology Center, Department of Cell Biology, Medical University of South Carolina, and Vasculogenix, Inc, Charleston, South Carolina 29425, USA.
Larue
Amanda C
AC
Fleming
Paul A
PA
Drake
Christopher J
CJ
D000482:Allantois / Q000098:blood supply* / Q000196:embryology; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001808:Blood Vessels / Q000166:cytology / Q000196:embryology* / Q000502:physiology; D002478:Cells, Cultured; D016228:Endothelial Growth Factors / Q000276:immunology / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000196:embryology / Q000502:physiology; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins / Q000276:immunology / Q000378:metabolism*; D008222:Lymphokines / Q000276:immunology / Q000378:metabolism*; D008648:Mesoderm / Q000166:cytology / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D018919:Neovascularization, Physiologic / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000276:immunology / Q000378:metabolism; D042442:Vascular Endothelial Growth Factors
D000906:Antibodies; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D040301:Vascular Endothelial Growth Factor Receptor-2