title: Cadherin-mediated cell adhesion is critical for the closing of the mouse optic fissure.
abstract: Coloboma is a congenital disease that contributes significantly to childhood blindness. It results from the failure in closing the optic fissure, a transient opening on the ventral side of the developing eye. Although human and mouse genetic studies have identified a number of genes associated with coloboma, the detailed cellular mechanisms underlying the optic fissure closure and coloboma formation remain largely undefined. N-cadherin-mediated cell adhesion has been shown to be important for the optic fissure closure in zebrafish, but it remains to be determined experimentally how cell-cell adhesions are involved in the mammalian optic fissure closing process. α-Catenin is required for cell adhesion mediated by all of the classic cadherin molecules, including N-cadherin. In this study, we used the Cre-mediated conditional knockout technique to specifically delete α-catenin from the developing mouse eye to show that it is required for the successful closing of the optic fissure. In α-catenin conditional mutant optic cups, the major cell fates, including the optic fissure margin, neural retina and retinal pigmented epithelium, are specified normally, and the retinal progenitor cells proliferate normally. However, adherens junctions components, including N-cadherin, β-catenin and filamentous actin, fail to accumulate on the apical side of α-catenin mutant retinal progenitor cells, where adherens junctions are normally abundant, and the organization of the neural retina and the optic fissure margin is disrupted. Finally, the α-catenin mutant retina gradually degenerates in the adult mouse eye. Therefore, our results show that α-catenin-mediated cell adhesion and cell organization are important for the fissure closure in mice, and further suggest that genes that regulate cell adhesion may underlie certain coloboma cases in humans.
authors.affiliation: Stowers Institute for Medical Research, Kansas City, Missouri, United States of America. sch@stowers.org
authors.forename: Shuyi
authors.initials: S
authors.lastname: Chen
authors.forename: Brandy
authors.initials: B
authors.lastname: Lewis
authors.forename: Andrea
authors.initials: A
authors.lastname: Moran
authors.forename: Ting
authors.initials: T
authors.lastname: Xie
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D022005:Adherens Junctions / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion; D002454:Cell Differentiation; D003103:Coloboma / Q000235:genetics / Q000378:metabolism; D005123:Eye / Q000254:growth & development / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009898:Optic Disk / Q000254:growth & development / Q000378:metabolism / Q000502:physiology; D012160:Retina / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000254:growth & development / Q000378:metabolism; D051178:alpha Catenin / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: D015820:Cadherins; D051178:alpha Catenin; D051176:beta Catenin