Notch signaling controls liver development by regulating biliary differentiation

Yiwei Zong; Archana Panikkar; Jie Xu; Aline Antoniou; Peggy Raynaud; Frederic Lemaigre; Ben Z. Stanger

doi:10.1242/dev.029140

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Notch signaling controls liver development by regulating biliary differentiation

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Notch signaling controls liver development by regulating biliary differentiation

Yiwei Zong, Archana Panikkar, Jie Xu, Aline Antoniou, Peggy Raynaud, Frederic Lemaigre et Ben Z. Stanger

Development (Cambridge), Vol.136(10), pp.1727-1739

15/05/2009

DOI: https://doi.org/10.1242/dev.029140

PMID: 19369401

Résumé

In the mammalian liver, bile is transported to the intestine through an intricate network of bile ducts. Notch signaling is required for normal duct formation, but its mode of action has been unclear. Here, we show in mice that bile ducts arise through a novel mechanism of tubulogenesis involving sequential radial differentiation. Notch signaling is activated in a subset of liver progenitor cells fated to become ductal cells, and pathway activation is necessary for biliary fate. Notch signals are also required for bile duct morphogenesis, and activation of Notch signaling in the hepatic lobule promotes ectopic biliary differentiation and tubule formation in a dose-dependent manner. Remarkably, activation of Notch signaling in postnatal hepatocytes causes them to adopt a biliary fate through a process of reprogramming that recapitulates normal bile duct development. These results reconcile previous conflicting reports about the role of Notch during liver development and suggest that Notch acts by coordinating biliary differentiation and morphogenesis.

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Détails

Titre: Notch signaling controls liver development by regulating biliary differentiation
Créateurs - sans rôle: Yiwei Zong - Division of Gastroenterology, Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, 512 BRB II/III, 421 Curie Boulevard, Philadelphia, PA 19104, USA. Université Catholique de Louvain and de Duve Institute, Avenue Hippocrate 75/7529, 1200 Brussels, Belgium
Archana Panikkar - Division of Gastroenterology, Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, 512 BRB II/III, 421 Curie Boulevard, Philadelphia, PA 19104, USA. Université Catholique de Louvain and de Duve Institute, Avenue Hippocrate 75/7529, 1200 Brussels, Belgium
Jie Xu - Division of Gastroenterology, Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, 512 BRB II/III, 421 Curie Boulevard, Philadelphia, PA 19104, USA. Université Catholique de Louvain and de Duve Institute, Avenue Hippocrate 75/7529, 1200 Brussels, Belgium
Aline Antoniou - Division of Gastroenterology, Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, 512 BRB II/III, 421 Curie Boulevard, Philadelphia, PA 19104, USA. Université Catholique de Louvain and de Duve Institute, Avenue Hippocrate 75/7529, 1200 Brussels, Belgium
Peggy Raynaud - Division of Gastroenterology, Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, 512 BRB II/III, 421 Curie Boulevard, Philadelphia, PA 19104, USA. Université Catholique de Louvain and de Duve Institute, Avenue Hippocrate 75/7529, 1200 Brussels, Belgium
Frederic Lemaigre - Division of Gastroenterology, Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, 512 BRB II/III, 421 Curie Boulevard, Philadelphia, PA 19104, USA. Université Catholique de Louvain and de Duve Institute, Avenue Hippocrate 75/7529, 1200 Brussels, Belgium
Ben Z. Stanger - Division of Gastroenterology, Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, 512 BRB II/III, 421 Curie Boulevard, Philadelphia, PA 19104, USA. Université Catholique de Louvain and de Duve Institute, Avenue Hippocrate 75/7529, 1200 Brussels, Belgium
Détails de publication: Development (Cambridge), Vol.136(10), pp.1727-1739
Éditeur: Company of Biologists
Nombre de pages: 13
Identifiants: 99149613609311
Unité académique: Centre de Recherche en Biologie Cellulaire de Montpellier - CRBM
Langue: English
Type de ressource: Journal article