Specific members of the Eph family of receptors and ligands have been shown to participate in angiogenesis, neural network development and axonal targeting. During development of the embryonic vasculature, EphB4 receptors are expressed on endothelial cells on arterial structures, while the ephrin-B ligand is restricted in expression to endothelium of the developing arterial vasculature. This laboratory has defined roles for EphB1 and ephrin B1 interactions in assembly of renal capillary microvasculature and in development of the glomerular microcirculation. Recent evidence has coupled receptor activation with activation of alphavbeta3 integrin has an important participant in tumor angiogenesis. This proposal addressed three aims to define functions of Eph receptors and ephrin ligands in the dermal microvasculature: 1) identify and characterize dermal capillary expression of Eph receptors and ephrin ligands using recombinant ectodomain fusions us high affinity binding reagents, 2) evaluate the dermal capillary expression of specific ephrins and EphB receptors in capillary endothelial cells marked by expression of beta-galactosidase under control of the flk-1 promoter, in models of wound healing and in response to sponges impregnated with ephrin ectodomains, and 3) establish transgenic mouse lines over- expressing ephrinB1/Fc (secreted) and ephrin1 (wt, transmembrane form) under control of the K14 epidermal basal keratinocyte promoter. These studies promise to evaluate effects of local over-expression on vascular structures and wound healing, and to define functions of this important ligand receptor system in the dermal microvasculature.
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