Platelet-derived growth factor (PDGF), a potent mitogen for mesenchymal cells in culture, is likely to be an important regulatory molecule in normal vertebrate development. PDGF is highly expressed in early vertebrate embryos. PDGF has a profound effect on several embryonic cell systems in vitro, suggesting that PDGF is important in cardiovascular, skeletal muscle, and central nervous system development. One way to establish the developmental function of PDGF is to interrupt growth factor receptor signalling in vivo. In our lab, a PDGF beta receptor mutant has recently been produced that inhibits wild-type beta receptor function in a dominant manner. This mutant receptor forms a dimer with wild-type receptor upon ligand stimulation, preventing subsequent signal transduction. In this proposal, the Xenopus PDGF receptors will be cloned and the spatial and temporal distribution of these receptors in embryonic development will be examined. Next, dominant negative Xenopus PDGF receptor mutants will be produced. Mutants will be introduced into early frog embryos by microinjection of receptor encoding mRNA. The effects of PDGF receptor inhibition during embryonic development will be assessed by morphologic analysis. These studies will help clarify the role of PDGF in embryogenesis. They will also provide a method to inhibit the action of PDGF in vivo and may therefore lead to the generation of therapeutic agents.
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