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Loss of ephrin-A5 function disrupts lens fiber cell packing and leads to cataract.


ABSTRACT: Cell-cell interactions organize lens fiber cells into highly ordered structures to maintain transparency. However, signals regulating such interactions have not been well characterized. We report here that ephrin-A5, a ligand of the Eph receptor tyrosine kinases, plays a key role in lens fiber cell shape and cell-cell interactions. Lens fiber cells in mice lacking ephrin-A5 function appear rounded and irregular in cross-section, in contrast to their normal hexagonal appearance in WT lenses. Cataracts eventually develop in 87% of ephrin-A5 KO mice. We further demonstrate that ephrin-A5 interacts with the EphA2 receptor to regulate the adherens junction complex by enhancing recruitment of beta-catenin to N-cadherin. These results indicate that the Eph receptors and their ligands are critical regulators of lens development and maintenance.

SUBMITTER: Cooper MA 

PROVIDER: S-EPMC2575469 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature

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Loss of ephrin-A5 function disrupts lens fiber cell packing and leads to cataract.

Cooper Margaret A MA   Son Alexander I AI   Komlos Daniel D   Sun Yuhai Y   Kleiman Norman J NJ   Zhou Renping R  

Proceedings of the National Academy of Sciences of the United States of America 20081023 43


Cell-cell interactions organize lens fiber cells into highly ordered structures to maintain transparency. However, signals regulating such interactions have not been well characterized. We report here that ephrin-A5, a ligand of the Eph receptor tyrosine kinases, plays a key role in lens fiber cell shape and cell-cell interactions. Lens fiber cells in mice lacking ephrin-A5 function appear rounded and irregular in cross-section, in contrast to their normal hexagonal appearance in WT lenses. Cata  ...[more]

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