Integrins and other receptors for extracellular matrix proteins such as fibronectin, vitronectin, and collagen are thought to play important roles in embryonic development, wound healing, and tumor cell metastasis. Recent studies suggest important roles for integrins in early development including neural crest migration, as well as keratinocyte migration during wound healing. Defects in integrin- related functions might contribute to a variety of human congenital defects involving mistakes in morphogenesis. Tissue-specific receptors are likely to provide a means of providing specificity of interactions with individual molecules such as fibronectin and collagen. Collaborative studies have identified unique and common features of fibronectin- and collagen-binding receptors from fibroblasts and platelets; these data may facilitate the development of tissue-specific inhibitors. Monoclonal antibody inhibition experiments with gingival keratinocytes established that specific integrin receptors are used for adhesion to fibronectin and collagen. The binding of antibodies to beta1 integrins stimulated the secretion of type IV collagenase by gingival keratinocytes, whereas binding of a variety of known integrin ligands did not. Integrin signalling may therefore help regulate secretion of an enzyme implicated in gingival wound healing. We are exploring various approaches to develop novel recombinant DNA and immunological probes against various integrin subunits to establish their roles in early development using animal models, including in the formation of craniofacial structures. Other studies will characterize the roles of the integrins and of cell-to-cell adhesion systems in mutual cross-regulation of function during morphogenesis and other developmental events.
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