Reiterative use of the notch signal during zebrafish intrahepatic biliary development.
Reiterative use of the notch signal during zebrafish intrahepatic biliary development.
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DOI：
10.1002/dvdy.22220
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发表时间：
2010-03
期刊：
影响因子：
--
通讯作者：
Pack M
中科院分区：
文献类型：
--
作者：
Lorent K;Moore JC;Siekmann AF;Lawson N;Pack M
Notch信号通路调节斑马鱼肝祖细胞向胆管细胞命运的特化。在这里，使用分阶段管理的药理学抑制剂的Notch受体处理，我们表明，激活的Notch途径也是重要的生长和扩大的肝内胆管网络在斑马鱼幼虫。胆管扩张伴随着广泛的细胞增殖和新生导管网络的主动重塑，如通过表达Notch响应性荧光报告基因转基因的活斑马鱼幼虫的延时成像所揭示的。总之，这些数据支持了一个模型，其中Notch信号在胆管发育过程中以粘附方式起作用;首先是特定的胆管细胞，然后是新生胆管网络的直接重塑。由于Notch途径在哺乳动物（包括人类）的胆道发育过程中发挥着类似的作用，因此这些研究也表明指导脊椎动物胆道发育的分子机制具有广泛的保守性。
The Notch signaling pathway regulates specification of zebrafish liver progenitor cells towards a biliary cell fate. Here, using staged administration of a pharmacological inhibitor of Notch receptor processing, we show that activation of the Notch pathway is also important for growth and expansion of the intrahepatic biliary network in zebrafish larvae. Biliary expansion is accompanied by extensive cell proliferation and active remodeling of the nascent ductal network, as revealed by time lapse imaging of living zebrafish larvae that express a Notch responsive fluorescent reporter transgene. Together, these data support a model in which the Notch signal functions reiteratively during biliary development; first to specific biliary cells and then to direct remodeling of the nascent biliary network. As the Notch pathway plays a comparable role during mammalian biliary development, including humans, these studies also indicate broad conservation of the molecular mechanisms directing biliary development in vertebrates.