Laminin-binding integrins in rat lens morphogenesis and their regulation during fibre differentiation

Mammalian lens development involves cell-cell and cell-ECM interactions. As integrins are a major family of cell adhesion molecules, we examined the expression patterns of several integrin subunits (α3A, α3B, α6A, α6B, β1 and β4) during rat lens development. RT-PCR, in situ hybridisation, immunofluorescence and immunoblotting were used to investigate expression of integrin subunits during lens development and differentiation. RT-PCR showed expression of α3A, α6A, α6B and β1A but not α3B or β4 subunits in postnatal rat lenses. Each subunit displayed distinct spatio-temporal expression patterns. β1 integrin was expressed in both epithelium and fibres. α3A subunit expression was restricted to the epithelium; expression ceased abruptly at the lens equator. Expression of the α6A subunit increased during fibre differentiation, whereas α6B expression was predominantly associated with epithelial cells during lens development. In lens epithelial explants, FGF induced some of the changes in integrin expression that are characteristic of fibre differentiation in vivo. One notable exception was the inability of FGF to reproduce the distinctive down-regulation of the α3 isoform that is associated with initiation of elongation in vivo. Interestingly, vitreous treatment was able to reproduce this shift in α3 expression indicating that another factor(s), in addition to FGF, may be required for full and complete transition from an epithelial cell to a fibre cell. Integrin subunit expression therefore appears to be highly regulated during lens development and fibre differentiation with evidence of major changes in α3 and α6 isoform expression. These results indicate that integrins may play important roles in development and growth of the lens. How specific integrin subunits influence the behaviour of cells in different developmental compartments of the lens remains to be determined.