Notch Signaling Controls Liver Development by Regulating Biliary Differentiation

Overview

Journal Development

Specialty Biology

Date 2009 Apr 17

PMID 19369401

Citations 225

Authors

Yiwei Zong

Archana Panikkar

Jie Xu

Aline Antoniou

Peggy Raynaud

Frederic Lemaigre

Ben Z Stanger

Affiliations

Soon will be listed here.

Abstract

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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