Morphogenesis and the response to injury by tissues both involve communication between cells and their microenvironment. The microenvironment is composed of soluble signals such as growth factors, and insoluble signals such as the extracellular matrix. These signals impart instructional information to cells through receptors that control pattern formation and the acquisition of specialized cell functions. The syndecan family of cell surface heparan sulfate proteoglycans bind to and mediate the action of several of these growth factors and extracellular matrix components. Thus, by changing the expression of syndecans, cells control their responsiveness to the microenvironment. Our prior work has shown that expression of two syndecan family members can be controlled by synducin, a unique protein that is released during wound repair. Our central hypothesis is that control of syndecan expression at the cell surface regulates cellular behaviors involved in morphogenesis and wound repair. Synducin, as an inducer of syndecans, can therefore influence cellular behaviors by control of syndecan expression. Synducin may also have other biological effects. This proposal seeks to change the normal expression of synducin in mice by a transgenic approach. This approach will evaluate the biological effects of synducin in vivo and may give insight into the significance of altered syndecan expression during injury and embryogenesis. Thus, our Specific Aims ar to: (i) Evaluate the functional consequences of over-expression of synducin in transgenic mice. (ii) Evaluate the functional consequences of tissue-specific overexpression of synducin in the skin of transgenic mice. (iii) Determine the genomic structure of synducin. (iv) Evaluate the functional consequences of targeted deletion of synducin.
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