| Differential requirement for beta-catenin in epithelial and fiber cells during lens development. | |
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MedLine Citation:
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PMID: 18652817 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't Date: 2008-07-09 |
Journal Detail:
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Title: Developmental biology Volume: 321 ISSN: 1095-564X ISO Abbreviation: Dev. Biol. Publication Date: 2008 Sep |
Date Detail:
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Created Date: 2008-09-15 Completed Date: 2008-10-27 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0372762 Medline TA: Dev Biol Country: United States |
Other Details:
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Languages: eng Pagination: 420-33 Citation Subset: IM |
Affiliation:
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Ocular Development Laboratory, Anatomy and Cell Biology Department, University of Melbourne, Victoria 3010, Australia. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adherens Junctions
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metabolism* Animals Cell Differentiation / physiology Cell Polarity / physiology Epithelial Cells / metabolism* Gene Expression Regulation, Developmental / physiology* Lens, Crystalline / embryology* Mice Signal Transduction / physiology* Wnt Proteins / metabolism* beta Catenin / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Wnt Proteins; 0/beta Catenin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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