Integrins are heterodimeric receptors which link the extracellular matrix to the cytoskeleton. They function beyond their role in adhesion, transmitting signals between the extracellular matrix (ECM) and the cell. Integrin mediated signalling has been shown to play a regulatory role in cellular differentiation. This grant focuses on the role of the integrin receptors, as both cell-substrate and cell-cell adhesion molecules, in lens development. Changes in integrin expression as a function of lens cell differentiation will be characterized in vivo. A chick embryo lens culture system will be used to characterize the mechanisms whereby i) integrins signal the initiation of lens differentiation and ii) changes in integrin interaction with the ECM regulates terminal lens differentiation. These lens cultures begin as an epithelial monolayer and differentiate to form multilayered lentoid structures. In the cultures the adhesion processes involved in lens differentiation can be manipulated both with antibodies to beta1 integrin and transformation with the src oncogene, both which result in a block of lens differentiation. I will examine the effects of antibodies to beta1 integrin and src on the organization of integrins in adhesion structures, on the association of cytoskeletal proteins with integrins in the adhesion structures and on the tyrosine phosphorylation of adhesion associated proteins. These studies will use immunocytochemical and biochemical techniques. Lens cultures transformed with the temperature sensitive src virus, tsLA24A, are a powerful tool for these studies in that they provide for the synchronous initiation of lens differentiation in culture. With the transformed lens cells it should be possible to describe the role of integrins in initiating and establishing the differentiation of lens cells in culture.
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