title: Differential requirement for beta-catenin in epithelial and fiber cells during lens development.
abstract: Recent studies implicate Wnt/beta-catenin signaling in lens differentiation (Stump, R. J., et al., 2003. A role for Wnt/beta-catenin signaling in lens epithelial differentiation. Dev Biol;259:48-61). Beta-catenin is a component of adherens junctions and functions as a transcriptional activator in canonical Wnt signaling. We investigated the effects of Cre/LoxP-mediated deletion of beta-catenin during lens development using two Cre lines that specifically deleted beta-catenin in whole lens or only in differentiated fibers, from E13.5. We found that beta-catenin was required in lens epithelium and during early fiber differentiation but appeared to be redundant in differentiated fiber cells. Complete loss of beta-catenin resulted in an abnormal and deficient epithelial layer with loss of E-cadherin and Pax6 expression as well as abnormal expression of c-Maf and p57(kip2) but not Prox1. There was also disrupted fiber cell differentiation, characterized by poor cell elongation, decreased beta-crystallin expression, epithelial cell cycle arrest at G(1)-S transition and premature cell cycle exit. Despite cell cycle arrest there was no induction of apoptosis. Mutant fiber cells displayed altered apical-basal polarity as evidenced by altered distribution of the tight junction protein, ZO1, disruption of apical actin filaments and abnormal deposition of extracellular matrix, resulting in a deficient lens capsule. Loss of beta-catenin also affected the formation of adhesion junctions as evidenced by dissociation of N-cadherin and F-actin localization in differentiating fiber cells. However, loss of beta-catenin from terminally differentiating fibers had no apparent effects on adhesion junctions between adjacent embryonic fibers. These data indicate that beta-catenin plays distinct functions during lens fiber differentiation and is involved in both Wnt signaling and adhesion-related mechanisms that regulate lens epithelium and early fiber differentiation.
authors.affiliation: Ocular Development Laboratory, Anatomy and Cell Biology Department, University of Melbourne, Victoria 3010, Australia.
authors.forename: Sarah
authors.initials: S
authors.lastname: Cain
authors.forename: Gemma
authors.initials: G
authors.lastname: Martinez
authors.forename: Maria I
authors.initials: MI
authors.lastname: Kokkinos
authors.forename: Kirsty
authors.initials: K
authors.lastname: Turner
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Richardson
authors.forename: Helen E
authors.initials: HE
authors.lastname: Abud
authors.forename: Joerg
authors.initials: J
authors.lastname: Huelsken
authors.forename: Michael L
authors.initials: ML
authors.lastname: Robinson
authors.forename: Robb U
authors.initials: RU
authors.lastname: de Iongh
mesh_terms: D022005:Adherens Junctions / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D016764:Cell Polarity / Q000502:physiology; D004847:Epithelial Cells / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D007908:Lens, Crystalline / Q000196:embryology*; D051379:Mice; D015398:Signal Transduction / Q000502:physiology*; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D051153:Wnt Proteins; D051176:beta Catenin