title: Role of β-catenin in development of bile ducts.
abstract: 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 β-catenin is dispensable for differentiation of liver precursor cells (hepatoblasts) to cholangiocyte precursors. Second, when β-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 β-catenin in cholangiocyte precursors perturbed duct development and cholangiocyte differentiation. We conclude that β-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.
authors: Université catholique de Louvain, de Duve Institute, Avenue Hippocrate 75/B1-7503, 1200 Brussels, Belgium.
authors: Sabine
authors: S
authors: Cordi
authors: Institut Cochin, INSERM U1016; CNRS, UMR8104; Equipe labellisée Ligue Nationale Contre le Cancer; Université Paris Descartes, 24 rue du Faubourg Saint-Jacques, 75014 Paris, France.
authors: Cécile
authors: C
authors: Godard
authors: Université catholique de Louvain, de Duve Institute, Avenue Hippocrate 75/B1-7503, 1200 Brussels, Belgium.
authors: Thoueiba
authors: T
authors: Saandi
authors: Université catholique de Louvain, de Duve Institute, Avenue Hippocrate 75/B1-7503, 1200 Brussels, Belgium.
authors: Patrick
authors: P
authors: Jacquemin
authors: Department of Pathology, Department of Medicine, University of Pittsburgh School of Medicine, 200 Lothrop St, Rm S-422 BST, Pittsburgh, PA 15261, USA.
authors: Satdarshan P
authors: SP
authors: Monga
authors: Institut Cochin, INSERM U1016; CNRS, UMR8104; Equipe labellisée Ligue Nationale Contre le Cancer; Université Paris Descartes, 24 rue du Faubourg Saint-Jacques, 75014 Paris, France.
authors: Sabine
authors: S
authors: Colnot
authors: Université catholique de Louvain, de Duve Institute, Avenue Hippocrate 75/B1-7503, 1200 Brussels, Belgium. Electronic address: frederic.lemaigre@uclouvain.be.
authors: Frédéric P
authors: FP
authors: Lemaigre
mesh_terms: D000818:Animals; D001652:Bile Ducts / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D008099:Liver / Q000254:growth & development* / Q000378:metabolism; D051379:Mice; D009024:Morphogenesis / Q000235:genetics*; D051176:beta Catenin / Q000235:genetics*
chemical_list: D051176:beta Catenin
keywords: Biliary tract; Cholangiocytes; Differentiation; Hepatocytes; Liver development; Morphogenesis