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G. F. Pontoriero, A. N. Smith, R. A. Lang, J. A. West-Mays; Co-Operative Roles for E and N-Cadherin During Vertebrate Lens Development. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5407. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Cell adhesion molecules are thought to play important roles in multiple aspects of lens development. Three cadherin molecules (E, N, and P) are expressed during embryonic lens development, but only E and N-cadherin are maintained in lens throughout the life of the lens. E-cadherin exhibits a lens epithelial cell-specific expression pattern, while N-cadherin is more broadly localized to both the epithelial and fibre cell compartments. Conditional deletion of either E or N-cadherin within the developing lens yields strikingly similar phenotypes and would suggest theses molecules possess redundant roles during lens development.
To critically analyze the co-requirement of E-cadherin and N-cadherin in lens morphogenesis, a mouse lacking both of these cadherin molecules within the developing lens and surface ectoderm was created using the Cre-loxP approach. Resultant mutant progeny (Le-Cre+;Cdh1KO/flox;Cdh2flox/flox) were compared with wildtype littermates in order to detect any significant morphological or immunohistochemical differences.
At P7, Le-Cre+;Cdh1KO/flox;Cdh2flox/flox double conditional knockout mice exhibited microphthalmia, and only remnants of lens material. The iris had also fused with the overlying cornea, which in turn lacked a distinct corneal epithelium and endothelium. Le-Cre+;Cdh1KO/flox;Cdh2flox/flox mutants also possessed a fully laminated retina that appeared overgrown and grossly misfolded. At early embryonic timepoints, Le-Cre+;Cdh1KO/flox; Cdh2flox/flox mice developed a lens placode that invaginated to form a lens vesicle. However, the lumen of this vesicle was composed of a number of cells that were immunoreactive to Pax6 and also TUNEL positive. While the primary fibre cells continued to develop as embryogenesis progressed in the double conditional mutants, a distinct lens epithelial layer failed to develop (Pax6 negative) at E15.5 and onward. Comparisons with littermates lacking various combinations of E and N-cadherin, also suggest that the dosage of cadherin molecules present within the lens epithelium is critical for proper development of the lens.
Progressive loss of the lens epithelial cell layer in the double Le-Cre+;Cdh1KO/flox;Cdh2flox/flox mutants indicates that E and N-cadherin have redundant roles in the development and maintenance of the lens epithelium.
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