First Author | Cheng C | Year | 2011 |
Journal | PLoS One | Volume | 6 |
Issue | 11 | Pages | e28147 |
PubMed ID | 22140528 | Mgi Jnum | J:316488 |
Mgi Id | MGI:6228542 | Doi | 10.1371/journal.pone.0028147 |
Citation | Cheng C, et al. (2011) Diverse roles of Eph/ephrin signaling in the mouse lens. PLoS One 6(11):e28147 |
abstractText | 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 beta-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 beta-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. |