The hyaluronate (HA) receptor is an integral membrane glycoprotein of 85 kDa, which is a member of the link-protein family of receptors. It has been implicated in a number of cellular processes, such as adhesion, migration and phagocytosis. Recent immunohistochemical studies of developing hamster embryos have revealed that the expression of the HA receptor is correlated with the development of the hair follicle, which involves a mesenchymal - epithelial interaction. More specifically, the receptor was present on the mesenchymal cells involved in the induction of hair follicles, but absent from interfollicular mesenchymal cells. In addition, it was expressed on the follicular mesenchymal cells only during inductive stages and was absent from these cells in the mature hair follicle. In contrast to the above, the distribution of HA was exactly reversed from that of the HA recaptor. HA was conspicuously absent from the regions of follicular mesenchymal cells as long as the receptor was expressed, and returned only after the recaptor disappeared. These observations form the basis of the following hypotheses: 1) the follicular mesenchymal cells possessing the recaptor are able to degrade HA in their immediate vicinity; 2) the localized loss of HA leads to the condensation of these follicular mesenchymal cells; 3) the loss of HA also induces a response in the adjacent epithelium to form a hair follicle. To test these hypotheses, embryos will be treated with various inhibitors of the receptor as well as with hyaluronidase, and then assessed histochemically. If the above hypotheses are correct, then the inhibitors should block the degradation of HA, the condensation of the mesenchymal cells, and the formation of the hair follicle. Similarly, hyaluronidase treatment should mimic the events in follicle formation. In addition, both HA and collagen will be examined at the ultrastructural level to determine if they play a role in induction. In several related experiments, the nature of the hair follicle formation will be examined. First, to determine if the growth of the follicle is due to increased proliferation or to cell migration, the rate of division of follicular epidermal cells will be examined. And secondly, the elongation of the follicle will be examined to determine whether it is due to the downward growth of the epidermis or to the upward expansion of the mesenchyme. This will be accomplished by culturing embryonic mesenchymal tissue in the absence of the epidermis, and determining the location of the mesenchymal condensations. The results of these studies should clarify the role of HA and its receptor in the formation of the hair follicle.
