During the development of the endocardium and vascular tree, cell-cell interactions play a crucial role in generating a complex pattern of cell types within the embryo. In one of the first patterning events in the embryo, a diffusible substance passes from the endoderm to the ectoderm to induce formation of mesoderm. Experimental evidence suggests that there are at least two signals emanating from endoderm: one specifying dorsal mesodermal derivatives such as notochord; and the second specifying ventral and lateral mesodermal derivatives such as mesenchyme and hemangioblastic tissues (blood, endothelium and endocardium). The heparin-binding growth factors, which include acidic and basic fibroblast growth factors (aFGF and bFGF), are known to participate in a variety of processes including mitogenesis, angiogenesis, wound healing and neuronal survival, and have also been implicated as ventral-type mesoderm inducers in amphibian embryos. We have cloned and characterized two different FGF receptor genes from Xenopus laevis (XFGFR1 and XFGFR2) and have shown that each has a distinct pattern of expression in the developing embryo. The long-term goal of this proposal is to identify the molecular mechanisms that regulate the differentiation of ventro-lateral mesoderm including vascular precursors. Since the FGFs have been shown to act as ventral-type mesoderm inducers, this proposal will focus on the role of FGF receptors in this process.
The specific aims of the proposal are: 1) to ectopically over-express wild-type and mutant mRNAs of XFGFR1 and XFGFR2 in developing Xenopus embryos; and 2) to identify, characterize and clone components of the XFGFR signal transduction pathway in developing Xenopus embryos. It is anticipated that this approach will result in elucidating some of the mechanisms by which the FGFs control the development of ventral mesoderm including precursors of the vasculature. The results obtained by this approach may then be applied to the analysis of these mechanisms in higher vertebrates.
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