Notch信号通路
生物
细胞生物学
形态发生
胆管
细胞命运测定
细胞分化
祖细胞
信号转导
内科学
干细胞
转录因子
遗传学
基因
医学
作者
Yiwei Zong,Archana Panikkar,Jie Xu,Aline Antoniou,Peggy Raynaud,Frédéric P. Lemaigre,Ben Z. Stanger
出处
期刊:Development
[The Company of Biologists]
日期:2009-05-15
卷期号:136 (10): 1727-1739
被引量:398
摘要
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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