A fundamental process in the formation of blood vessels (vasculogenesis)is the fusion of networks of endothelial tubes to form larger vessels. This process occurs throughout embryonic development and is perhaps best illustrated in the formation of the individual dorsal aortae from networks of endothelial tubes present along the embryonic axis. The mechanism underlying this fusion process is unknown. Exogenously introduced vascular endothelial cell growth factor (VEGF) can promote hyperfusion of networks. Hyperfusion is a process in which microvessels fuse excessively. This along with the finding that VEGF and its receptors are present in vasculogenic regions of the embryo suggest that the bioavailability of VEGF is strictly regulated during vascular development. Experiments are designed to substantiate the role of VEGF as an in vivo regulator of vascular fusion. A major feature of the proposed experiments is that they will be done in vivo, in the context of well characterized vascularizing regions. The role of VEGF will be evaluated by a series of experiments in which antagonists of the VEGF receptor interactions will be used to perturb the normal pattern of vasculogenesis. Results from this work will likely contribute to a greater understanding of vessel formation as it occurs not only in embryonic development but also in wound healing, and angiogenesis-related diseases such as ocular neovascularization, tumor growth, and hemangiomas.
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| Gentile, Carmine; Fleming, Paul A; Mironov, Vladimir et al. (2008) VEGF-mediated fusion in the generation of uniluminal vascular spheroids. Dev Dyn 237:2918-25 |
| Drake, Christopher J; Fleming, Paul A; Argraves, W Scott (2007) The genetics of vasculogenesis. Novartis Found Symp 283:61-71;discussion 71-6, 238-41 |
| LaRue, Amanda C; Masuya, Masahiro; Ebihara, Yasuhiro et al. (2006) Hematopoietic origins of fibroblasts: I. In vivo studies of fibroblasts associated with solid tumors. Exp Hematol 34:208-18 |
| Ebihara, Yasuhiro; Masuya, Masahiro; Larue, Amanda C et al. (2006) Hematopoietic origins of fibroblasts: II. In vitro studies of fibroblasts, CFU-F, and fibrocytes. Exp Hematol 34:219-29 |
| Drake, Christopher J; Wessels, Andy; Trusk, Tom et al. (2006) Elevated vascular endothelial cell growth factor affects mesocardial morphogenesis and inhibits normal heart bending. Dev Dyn 235:10-8 |
| Visconti, Richard P; Ebihara, Yasuhiro; LaRue, Amanda C et al. (2006) An in vivo analysis of hematopoietic stem cell potential: hematopoietic origin of cardiac valve interstitial cells. Circ Res 98:690-6 |
| Argraves, W Scott; Drake, Christopher J (2005) Genes critical to vasculogenesis as defined by systematic analysis of vascular defects in knockout mice. Anat Rec A Discov Mol Cell Evol Biol 286:875-84 |
| Abe, Takanori; Fleming, Paul A; Masuya, Masahiro et al. (2005) Granulocyte/macrophage origin of glomerular mesangial cells. Int J Hematol 82:115-8 |
| Ishikawa, Fumihiko; Drake, Christopher J; Yang, Su et al. (2003) Transplanted human cord blood cells give rise to hepatocytes in engrafted mice. Ann N Y Acad Sci 996:174-85 |
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