The role of β1-integrin and its ligands in lens development and disease
Date
2015
Authors
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Journal ISSN
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Publisher
University of Delaware
Abstract
This study has examined the fundamental cell biological processes that β1 integrins and their ligands control in the lens. I have demonstrated that β1 integrins play a vital role in the determination of cell fate during early lens development by modulating the activation of BMP and FGF signaling pathways. These observations highlight the temporal complexity in β1 integrin function during development. Further, the β1 integrin ligand, laminin- subunit lamα1, is essential for the formation of the lens capsule including the deposition of collagen IV into the capsule and thus lens morphology/structure. Further, lamα1 is essential for the organization of the corneal epithelium including deposition of TGFβi underneath the corneal epithelium. These data suggest that the lama1a69/a69 (lamα1) mutant phenotype is due to a combination of both a structural and signaling function of the lens capsule and early corneal epithelial BM (basement membrane) during early eye development (Pathania, Semina et al. 2014). Lastly I have shown that another β1 integrin ligand cFN (cellular fibronectin), similar to β1 integrins, may have a temporal complexity of function as well. While it appears to be essential for lens morphology in the early stages of lens development, its function is dispensable in a mature lens. However cFN is required for lens epithelial cells to undergo EMT during the late wound healing response following lens injury or cataract surgery. Notably, I have shown that cFN is required for TGFβ induced EMT signaling following lens injury or surgery.