title: Diverse roles of Eph/ephrin signaling in the mouse lens.
abstract: Recent genetic studies show that the Eph/ephrin bidirectional signaling pathway is associated with both congenital and age-related cataracts in mice and humans. We have investigated the molecular mechanisms of cataractogenesis and the roles of ephrin-A5 and EphA2 in the lens. Ephrin-A5 knockout ⁻/⁻ mice often display anterior polar cataracts while EphA2⁻/⁻ lenses show very mild cortical or nuclear cataracts at weaning age. The anterior polar cataract of ephrin-A5⁻/⁻ lenses is correlated with multilayers of aberrant cells that express alpha smooth muscle actin, a marker for mesenchymal cells. Only select fiber cells are altered in ephrin-A5⁻/⁻ lenses. Moreover, the disruption of membrane-associated β-catenin and E-cadherin junctions is observed in ephrin-A5⁻/⁻ lens central epithelial cells. In contrast, EphA2⁻/⁻ lenses display normal monolayer epithelium while disorganization is apparent in all lens fiber cells. Immunostaining of ephrin-A5 proteins, highly expressed in lens epithelial cells, were not colocalized with EphA2 proteins, mainly expressed in lens fiber cells. Besides the previously reported function of ephrin-A5 in lens fiber cells, this work suggests that ephrin-A5 regulates β-catenin signaling and E-cadherin to prevent lens anterior epithelial cells from undergoing the epithelial-to-mesenchymal transition while EphA2 is essential for controlling the organization of lens fiber cells through an unknown mechanism. Ephrin-A5 and EphA2 likely interacting with other members of Eph/ephrin family to play diverse functions in lens epithelial cells and/or fiber cells.
authors.affiliation: School of Optometry and Vision Science Program, University of California, Berkeley, California, United States of America.
authors.forename: Catherine
authors.initials: C
authors.lastname: Cheng
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Gong
mesh_terms: D000818:Animals; D057866:Anterior Capsule of the Lens / Q000378:metabolism / Q000473:pathology; D015820:Cadherins / Q000378:metabolism; D002386:Cataract / Q000378:metabolism / Q000473:pathology; D036386:Ephrin-A5 / Q000172:deficiency / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007908:Lens, Crystalline / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D010641:Phenotype; D021381:Protein Transport; D036104:Receptor, EphA2 / Q000172:deficiency / Q000378:metabolism*; D036081:Receptors, Eph Family / Q000378:metabolism*; D015398:Signal Transduction; D051176:beta Catenin / Q000378:metabolism
chemical_list: D015820:Cadherins; D036386:Ephrin-A5; D051176:beta Catenin; D049452:Green Fluorescent Proteins; D036104:Receptor, EphA2; D036081:Receptors, Eph Family