DEVELOPMENTAL HEMATO-ENDOTHELIAL BIOLOGY OF P1H12

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The apparent linkage between embryologic development of endothelial cells (EC) and hematopoiesis is a poorly understood but fundamental aspect of developmental biology. Our preliminary data indicate that P1H12-antigen is an EC-EC adhesion molecule, is expressed extremely early in embryogenesis, and probably marks embryonic cells having both hematopoietic and EC lineage potential. We hypothesize that P1H12 is a marker of the hemangioblast and plays a role in the earliest stages of vasculogenesis. We propose to study the biology of P1H12 by addressing five interrelated specific aims. (1) We will identify the mechanism by which P1H12 mediates EC-EC adhesion by identifying P1H12's binding partner and binding domains. (2) We will determine whether P1H12 is a marker of the putative hemangioblast, conducting differentiation studies in embryoid bodies in vitro and lineage-potential studies in murine embryos. (3) We will document the murine embryologic expression of P1H12 and define the phenotype of its absent expression, using standard techniques of histology, immuno-histochemistry, and in situ hybridization. (4) We will define the differentiation potential of P1H12's positive cells found in adult bone marrow, using culture systems to determine their lineage outgrowth potential. (5) We will define the differentiation potential of P1H12 positive cells found in peripheral blood, using various culture systems to define their lineage-outgrowth potential. These studies represent a first step towards defining the role of P1H12 in embryology, with an emphasis on hematopoiesis and vasculogenesis (as rationalized by exciting preliminary data).