Document Detail


Regulation of intrahepatic biliary duct morphogenesis by Claudin 15-like b.
MedLine Citation:
PMID:  22020048     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The intrahepatic biliary ducts transport bile produced by the hepatocytes out of the liver. Defects in biliary cell differentiation and biliary duct remodeling cause a variety of congenital diseases including Alagille Syndrome and polycystic liver disease. While the molecular pathways regulating biliary cell differentiation have received increasing attention (Lemaigre, 2010), less is known about the cellular behavior underlying biliary duct remodeling. Here, we have identified a novel gene, claudin 15-like b (cldn15lb), which exhibits a unique and dynamic expression pattern in the hepatocytes and biliary epithelial cells in zebrafish. Claudins are tight junction proteins that have been implicated in maintaining epithelial polarity, regulating paracellular transport, and providing barrier function. In zebrafish cldn15lb mutant livers, tight junctions are observed between hepatocytes, but these cells show polarization defects as well as canalicular malformations. Furthermore, cldn15lb mutants show abnormalities in biliary duct morphogenesis whereby biliary epithelial cells remain clustered together and form a disorganized network. Our data suggest that Cldn15lb plays an important role in the remodeling process during biliary duct morphogenesis. Thus, cldn15lb mutants provide a novel in vivo model to study the role of tight junction proteins in the remodeling of the biliary network and hereditary cholestasis.
Authors:
Isla D Cheung; Michel Bagnat; Taylur P Ma; Anirban Datta; Kimberley Evason; John C Moore; Nathan D Lawson; Keith E Mostov; Cecilia B Moens; Didier Y R Stainier
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-10-12
Journal Detail:
Title:  Developmental biology     Volume:  361     ISSN:  1095-564X     ISO Abbreviation:  Dev. Biol.     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2011-12-05     Completed Date:  2012-02-01     Revised Date:  2013-08-30    
Medline Journal Info:
Nlm Unique ID:  0372762     Medline TA:  Dev Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  68-78     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
Affiliation:
Department of Biochemistry and Biophysics, Program in Developmental and Stem Cell Biology, and Institute for Regeneration Medicine, University of California, San Francisco, CA 94158, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Bile Ducts, Intrahepatic / cytology,  growth & development*,  metabolism
Cell Line
Cell Polarity / physiology
Claudins / genetics,  metabolism*
Dogs
Epithelial Cells / metabolism
Fluorescent Antibody Technique
Hepatocytes / metabolism*
In Situ Hybridization
Larva / growth & development,  metabolism
Microscopy, Electron, Transmission
Morphogenesis / physiology*
Mutation / genetics
Tight Junctions / metabolism*
Zebrafish / growth & development*,  metabolism
Zebrafish Proteins / genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
5R01 DK074398/DK/NIDDK NIH HHS; DK060322/DK/NIDDK NIH HHS; DP2-3034656/DP/NCCDPHP CDC HHS; HG002995/HG/NHGRI NIH HHS; HL093467/HL/NHLBI NIH HHS; P30 CA015704/CA/NCI NIH HHS; P30 DK026743-30/DK/NIDDK NIH HHS; R01 DK060322-10/DK/NIDDK NIH HHS; R01 DK060322-10S1/DK/NIDDK NIH HHS; R01 HD076585/HD/NICHD NIH HHS; T32 HD007470-17/HD/NICHD NIH HHS; //Howard Hughes Medical Institute
Chemical
Reg. No./Substance:
0/Claudins; 0/Zebrafish Proteins; 0/claudin 15-like b protein, zebrafish
Comments/Corrections

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