Integrins and other cell surface receptors for extracellular matrix proteins such as fibronectin and vitronectin play roles in embryonic development and wound healing. Our studies suggest important roles for integrins in early development, such as during tooth morphogenesis and neural crest cell migration. Defects in integrin-related functions may contribute to a variety of human congenital defects involving mistakes in morphogenesis, as well as contributing to poor wound healing. Recent studies in progress have identified unexpectedly rapid and precise changes in expression of mRNA for the beta5 integrin during mouse molar development. Large, stage-specific changes in beta5 mRNA levels were detected, with alternation of expression between epithelium and mesenchyme within a single day. Such major regulatory switching is unprecedented for integrins, and it suggests interesting regulatory roles during tooth development. Adult keratinocytes are activated for adhesion and migration during the process of wound repair. Collaborative studies show that novel glycosylation changes in integrins accompany this process, which can be mediated by serum factors. Inhibition of beta1 integrin function in keratinocytes leads to disruption of actin cytoskeletal organization, even though cadherin cell adhesion molecules are apparently unaffected in distribution. This result provides an approach to understanding the functional roles of the actin scaffolding in cells by selective perturbation. In an ongoing reagent development program, we have developed novel recombinant DNA and immunological probes against various integrin subunits and their ligands to be able to test their roles in early development using animal models, e.g. in the formation of craniofacial structures. New mouse cDNA probes are now available for alpha-v, beta3, beta5, beta6, and other integrins, as well as for murine fibronectin and vitronectin. New antibody probes for alpha3 integrin and vitronectin are also being characterized. Other studies will characterize the mutual cross-regulation of function of integrin and cadherin adhesion systems during morphogenesis and other developmental events.
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