Journal
DIFFERENTIATION
Volume 91, Issue 1-3, Pages 42-49Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.diff.2016.02.001
Keywords
Liver development; Biliary tract; Cholangiocytes; Hepatocytes; Differentiation; Morphogenesis
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Funding
- Interuniversity Attraction Pole Programme (Belgian Science Policy (BELSPO)) [PVII-47]
- D.G. Higher Education and Scientific Research of the French Community of Belgium [10/15-029]
- Alphonse and Jean Forton Fund
- Fonds de la Recherche Scientifique Medicale [3.4536.10]
- Ligue Nationale Contre le Cancer (France)
- NIH [1RO1DK100287, 1RO1DK62277]
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Beta-catenin is known to play stage- and cell-specific functions during liver development. However, its role in development of bile ducts has not yet been addressed. Here we used stage-specific in vivo gain-and loss-of-function approaches, as well as lineage tracing experiments in the mouse, to first demonstrate that beta-catenin is dispensable for differentiation of liver precursor cells (hepatoblasts) to cholangiocyte precursors. Second, when beta-catenin was depleted in the latter, maturation of cholangiocytes, bile duct morphogenesis and differentiation of periportal hepatocytes from cholangiocyte precursors was normal. In contrast, stabilization of beta-catenin in cholangiocyte precursors perturbed duct development and cholangiocyte differentiation. We conclude that beta-catenin is dispensable for biliary development but that its activity must be kept within tight limits. Our work is expected to significantly impact on in vitro differentiation of stem cells to cholangiocytes for toxicology studies and disease modeling. (C) 2016 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.
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