Journal
DEVELOPMENTAL BIOLOGY
Volume 361, Issue 1, Pages 68-78Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ydbio.2011.10.004
Keywords
Claudin; Liver development; Zebrafish; Biliary duct remodeling; Biliary cells; Biliary duct morphogenesis; Tight junctions; Cholestasis
Categories
Funding
- ARCS Foundation
- NIH [DP2-3034656, HL093467, HG002995, DK060322]
- Damon Runyon Cancer Research Foundation [109-10]
- Pathology & Imaging Core of the UCSF Liver Center [P30 DK026743]
- Packard Foundation
- [5R01 DK074398]
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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. (C) 2011 Elsevier Inc. All rights reserved.
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