Thomas Poole, PhD
Vasculogenesis, Angiogenesis and Endothelial Cell Differentiation.
The embryonic vasculature forms by the segregation, migration and assembly of angioblasts from mesoderm, a process termed vasculogenesis. Angiogenesis continues vascular development by forming new vessels by sprouting from preexisting vessels. Two growth factors that play important roles in angioblast differentiation and vessel assembly are basic fibroblast growth factor (FGF-2) and vascular endothelial growth factor (VEGF). Our hypothesis is that FGF induces angioblast differentiation and both FGF and VEGF play major roles in the further growth and morphogenesis of angioblasts into the initial vascular pattern. Angioblasts in quail embryos and in quail/chick chimeras can be visualized using the monoclonal antibody, QH-1. The classic embryological technique of microsurgical transplantation will be used in combination with modern immunohistochemistry and molecular biology to perturb vasculogenesis and angiogenesis. Small beads and transfected mammalian cells will be used to deliver biologically relevant quantities of FGF and VEGF in the embryo during dorsal aorta formation. The experiments will reveal the cellular basis of these growth factorsí actions on endothelial cells and their precursors. Finally, arsenic perturbation of the vascular pattern is being studied because of its known toxic effects on the vascular system. Arsenic exposure appears to produce hypervascular embryos by upregulating VEGF expression.
Coffin, J. D. and T.J. Poole: Endothelial cell origin and migration in embryonic heart and cranial blood vessel development. Anatomical Record 231:383-395, 1991.
Spence, S.G. and T.J. Poole: Developing blood vessels and associated extracellular matrix as substrates for neural crest migration in Japanese quail, Coturnix coturnix japonica. International J. Developmental Biology 38:85-98, 1994.
Cox, C. M. and T. J. Poole: Angioblast differentiation is influenced by the local environment: FGF-2 induces angioblasts and patterns vessel formation in the quail embryo. Developmental Dynamics 218:371-382, 2000.
Poole, T.J., E.B. Finkelstein, and C.M. Cox: The role of FGF and VEGF in angioblast induction and migration during vascular development. Developmental Dynamics 220:1-17, 2001.
Finkelstein, E.B. and T.J. Poole: Vascular endothelial growth factor: a regulator of vascular morphogenesis in the japanese quail embryo. The Anatomical Record Part A 272A: 403-414, 2003.