Gene Regulation And Function Of Basement Membranes

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Basement membranes are thin extracellular matrices that separate cells, such as endothelial, epithelial, muscular, and neural cells, from their adjacent stroma. Basement membranes are the first extracellular matrix to appear in development and are degraded and regenerated during development and tissue repair. They not only provide the scaffold for cells and cell layers, but they also have an essential role in morphogenesis that affects cell adhesion, migration, proliferation, and differentiation. Additionally, basement membranes provide major barriers in blood vessels to the passage of proteins and invasion by metastatic tumor cells. The thickness and components of basement membranes are different in various tissues, suggesting tissue-specific functions. The major molecules in basement membranes are collagen IV, laminin, perlecan, and nidogen/entactin, which interact with each other to form the supramolecular structure. Recently, genetic diversity in the subunits of laminin and type IV collagen has been found and the existence of a large family of these molecules has been demonstrated. Our primary objectives have been to identify the specific functions of basement membrane components, to study the structure and function relationships, to elucidate the mechanisms by which they are regulated, and to describe related protein interactions in development and diseases. Our effort has also focused on establishing animal models to study functions of basement membrane components in development and disease and on creating therapeutic reagents for diseases associated with basement membranes. We have also identified bioactive sites on laminin that have a number of biological activities, such as promoting cell adhesion, migration, and neurite outgrowth, and affecting metastatic activity of tumor cells. These studies are aimed towards developing reagents useful for diagnostic and therapeutic applications.