Conditional deletion of beta1-integrin from the developing lens leads to loss of the lens epithelial phenotype.
Beta1-integrins are cell surface receptors that participate in sensing the cell's external environment. We used the Cre-lox system to delete beta1-integrin in all lens cells as the lens vesicle transitions into the lens. Adult mice lacking beta1-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 beta1-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 Prox1 and downregulate Pax6 levels demonstrating that beta1-integrin is essential to maintain the lens epithelial phenotype. Furthermore, beta1-integrin null lens epithelial cells upregulate the expression of alpha-smooth muscle actin and nuclear Smad4 and downregulate Smad6 suggesting that beta1-integrin may brake TGFbeta family signaling leading to epithelial-mesenchymal transitions in the lens. In contrast, beta1-integrin null lens epithelial cells show increased E-cadherin immunoreactivity which supports the proposed role of beta1-integrins in mediating complete EMT in response to TGFbeta family members. Thus, beta1-integrin is required to maintain the lens epithelial phenotype and block inappropriate activation of some aspects of the lens fiber cell differentiation program.
Simirskii
Vladimir N
VN
Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA.
Wang
Yan
Y
Duncan
Melinda K
MK
D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D003459:Crystallins / Q000378:metabolism; D004848:Epithelium / Q000196:embryology* / Q000378:metabolism; D017353:Gene Deletion; D006720:Homozygote; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D019012:Integrin beta1 / Q000235:genetics*; D007908:Lens, Crystalline / Q000196:embryology*; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype
D003459:Crystallins; D019012:Integrin beta1