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Regulation of intrahepatic biliary duct morphogenesis by Claudin 15-like b.

Developmental biology | Jan 1, 2012

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.

Pubmed ID: 22020048 RIS Download

Mesh terms: Animals | Bile Ducts, Intrahepatic | Cell Line | Cell Polarity | Claudins | Dogs | Epithelial Cells | Fluorescent Antibody Technique | Hepatocytes | In Situ Hybridization | Larva | Microscopy, Electron, Transmission | Morphogenesis | Mutation | Tight Junctions | Zebrafish | Zebrafish Proteins

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Associated grants

  • Agency: NIDDK NIH HHS, Id: 5R01 DK074398
  • Agency: NIDDK NIH HHS, Id: DK060322
  • Agency: NCCDPHP CDC HHS, Id: DP2-3034656
  • Agency: NHGRI NIH HHS, Id: HG002995
  • Agency: NHLBI NIH HHS, Id: HL093467
  • Agency: NCI NIH HHS, Id: P30 CA015704
  • Agency: NIDDK NIH HHS, Id: P30 DK026743
  • Agency: NIDDK NIH HHS, Id: P30 DK026743-30
  • Agency: NIDDK NIH HHS, Id: R01 DK060322
  • Agency: NIDDK NIH HHS, Id: R01 DK060322-10
  • Agency: NIDDK NIH HHS, Id: R01 DK060322-10S1
  • Agency: NICHD NIH HHS, Id: R01 HD076585
  • Agency: NICHD NIH HHS, Id: T32 HD007470
  • Agency: NICHD NIH HHS, Id: T32 HD007470-17
  • Agency: Howard Hughes Medical Institute, Id:

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