Integrins transduce both internal signals and signals from the matrix. These interactions between integrins, their extracellular matrix ligands, and their cytoskeletal partners play an important role in the regulation of cellular differentiation. We have shown them to be important in lens cell differentiation. In the lens capsule there is a compartmentalization of matrix components with fibronectin, primarily localized to the anterior capsule, and tenascin in the posterior capsule. Integrins are developmentally regulated in the lens. alpha 5 beta 1 integrin, like fibronectin, is primarily associated with the lens epithelial cells, where together they are likely to be important in regulation of adhesion and proliferation. alpha 6A beta 1, the integrin laminin receptor, is expressed at its highest levels in the equatorial epithelium and the peripheral fiber cells, both migratory populations. Because laminin is uniformly distributed in the lens capsule, such changes in alpha 6A integrin expression are likely critical to the cell's ability to regulate its response to laminin in the matrix. The organization of cytoskeletal molecules associated with the integrin cytoplasmic face also changes with development. In the epithelial regions of the lens, where the initiation of lens cell differentiation occurs, expression of the cytoskeletal proteins involved in cell-substrate interactions, talin, alpha-actinin, and the signaling proteins, are high. In the fiber cell region of the lens, where the cells establish stable cell-cell contacts, vinculin predominates and becomes highly associated with the cytoskeletal fraction. The role of integrins in lens development is not only regulated by changes in the expression of different integrin receptors but is also closely correlated with the expression and organization of the molecules with which they associate.