Conditional deletion of β1-integrin from the developing lens leads to loss of the lens epithelial phenotype

beta 1-integrins are cell surface receptors that participate in sensing the cell's external environment. We used the Cre-lox system to delete beta 1-integrin in all lens cells as the lens vesicle transitions into the lens. Adult mice lacking beta 1-integrin in the lens are microphthalmic due to apoptosis of the lens epithelium and neonatal disintegration of the lens fibers. The first morphological alterations in beta 1-integrin null lenses are seen at 16.5 dpc when the epithelium becomes disorganized and begins to upregulate the fiber cell markers beta- and gamma-crystallins, the transcription factors cMaf and Prox I and downregulate Pax6 levels demonstrating that beta 1-integrin is essential to maintain the lens epithelial phenotype. Furthermore, beta 1-integrin null lens epithelial cells upregulate the expression of alpha-smooth muscle actin and nuclear Smad4 and downregulate Smad6 suggesting that beta-integrin may brake TGF beta family signaling leading to epithelial-mesenchymal transitions in the lens. In contrast, beta 1-integrin null lens epithelial cells show increased E-cadherin immunoreactivity which supports the proposed role of beta 1-integrins in mediating complete EMT in response to TGF beta family members. Thus, beta 1-integrin is required to maintain the lens epithelial phenotype and block inappropriate activation of some aspects of the lens fiber cell differentiation program. (C) 2007 Elsevier Inc. All rights reserved.