Role of ß1-Containing Integrins in Cutaneous Basement Membrane Organization

In the mammalian epidermis cell-cell adhesion, cell migration and basement membrane (BM) assembly and organization are central to many biological and pathological processes. Recent genetic and cell-biological studies and, an elegant blend of classical and reverse genetics have illustrated the importance of basement membrane architecture and its cellular interactions in organogenesis of the epidermis and hair follicle, wound healing, tumorigenesis and skin blistering disorders. While important roles of basement membrane during development, such as establishing cellular polarity, promoting cell adhesion and cell survival have recently been elucidated, less is known about the dynamics of basement membrane assembly in vivo. 

The objective of our proposed study is to investigate how the different epithelial integrins and their downstream signaling effectors regulate the process of basement membrane assembly/organization and cell-substratum adhesion. Previously we generated the conditional knockout (KO) of integrin ß1 in the epidermis and successfully established the ß1 KO cells in culture. This provides us with a unique model system, which will be used to specifically address the role of ß1 and the other compensatory epithelial integrins in these important cellular processes.