Hyaluronate-cell interactions and growth factor regulation of hyaluronate synthesis during limb development.

Hyaluronate is a major component of the intercellular matrix surrounding proliferating and migrating cells in embryonic tissues. When placed in culture, mesodermal cells from the early, proliferative stages of limb development produce high levels of hyaluronate and exhibit prominent hyaluronate-dependent pericellular coats. Cells from the subsequent stages of mesodermal condensation that precede differentiation to cartilage and muscle produce less hyaluronate and do not exhibit these coats. Also at this time, binding sites specific for hyaluronate appear on the surface of the mesodermal cells. These binding sites may participate in the mechanism of condensation by mediating cell aggregation and the endocytosis of hyaluronate. Further changes in hyaluronate-cell interaction occur during differentiation of the condensed mesoderm to cartilage and muscle. Hyaluronate synthesis and pericellular coat formation in the mesoderm are stimulated by a factor, related to transforming growth factor-beta, that is produced by the surrounding ectoderm. The early limb also contains high levels of basic fibroblast growth factor. Its concentration is highest at the earliest stages, when cell proliferation and hyaluronate synthesis are prominent activities, and this factor has been shown to stimulate both these activities in cultures of limb mesodermal cells. Thus fibroblast growth factor and transforming growth factor-beta may be important in the regulation of early growth and morphogenesis of the limb.