Document Detail

Differential requirement for beta-catenin in epithelial and fiber cells during lens development.
MedLine Citation:
PMID:  18652817     Owner:  NLM     Status:  MEDLINE    
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.
Sarah Cain; Gemma Martinez; Maria I Kokkinos; Kirsty Turner; Robert J Richardson; Helen E Abud; Joerg Huelsken; Michael L Robinson; Robb U de Iongh
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-07-09
Journal Detail:
Title:  Developmental biology     Volume:  321     ISSN:  1095-564X     ISO Abbreviation:  Dev. Biol.     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-09-15     Completed Date:  2008-10-27     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372762     Medline TA:  Dev Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  420-33     Citation Subset:  IM    
Ocular Development Laboratory, Anatomy and Cell Biology Department, University of Melbourne, Victoria 3010, Australia.
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MeSH Terms
Adherens Junctions / metabolism*
Cell Differentiation / physiology
Cell Polarity / physiology
Epithelial Cells / metabolism*
Gene Expression Regulation, Developmental / physiology*
Lens, Crystalline / embryology*
Signal Transduction / physiology*
Wnt Proteins / metabolism*
beta Catenin / metabolism*
Reg. No./Substance:
0/Wnt Proteins; 0/beta Catenin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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