Early limb bud development begins by proliferation of mesodermal cells. These cells then condense in those areas that will later differentiate to muscle or cartilage cells, while the peripheral fibrogenic areas remain non-condensed. The mesodermal cells in the very early limb, and in the non-condensed areas subsequently, are separated by hydrated hyaluronate-enriched spaces. Hyaluronate synthesis has been associated with cell proliferation in several systems and thus we propose to examine the regulation of both hyalu-ronate synthesis and proliferation by two factors which we have recently shown to be present in the early limb bud. The factors are fibroblast growth factor and an ectodermal factor which stimulates mesodermal hyaluronate synthesis. We will produce monoclonal antibodies to both and use these to test the relationship between the two factors and between the regulation of hyaluronate synthesis, its interaction with the cell surface and cell proliferation. In future studies, we will employ the antibodies for immunolocalization, and development of sensitive assays for production of cDNA probes and examination of structure and synthesis of the factors. These studies will provide the basis for elucidation of aberrations in matrix synthesis and cell proliferation in limb deformities arising from genetic and teratological causes.
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