Bmp2 signaling regulates the hepatic versus pancreatic fate decision.
Bmp2 signaling regulates the hepatic versus pancreatic fate decision.
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DOI：
10.1016/j.devcel.2008.08.019
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发表时间：
2008-11
影响因子：
11.8
通讯作者：
Stainier, Didier Y. R.
中科院分区：
文献类型：
--
作者：
Chung, Won-Suk;Shin, Chong Hyun;Stainier, Didier Y. R.
外植体培养数据表明肝脏和胰腺起源于共同的祖细胞。我们在斑马鱼中使用单细胞谱系追踪来研究这个问题，并分析肝脏和胰腺的命运决定。在早期，离中线至少两个细胞的内胚层细胞可分化为肝脏和胰腺。相比之下，靠近中线的内胚层细胞产生胰腺和肠，但不产生肝脏。功能缺失和功能获得分析表明，在侧板中胚层表达的Bmp2b通过Alk8信号诱导内胚层细胞成为肝脏。当Bmp2b过表达时，位于中间的内胚层细胞，注定成为胰腺和肠，对肝脏有贡献。这些数据为肝胰腺双电位祖细胞的存在提供了体内证据，并表明它们的命运受内胚层的中外侧模式调节，这一过程由Bmp2b控制。
Explant culture data have suggested that the liver and pancreas originate from common progenitors. We used single cell lineage tracing in zebrafish to investigate this question in vivo as well as to analyze the hepatic vs pancreatic fate decision. At early somite stages, endodermal cells located at least two cells away from the midline can give rise to both liver and pancreas. In contrast, endodermal cells closer to the midline give rise to pancreas and intestine, but not liver. Loss- and gain-of-function analyses show that Bmp2b, expressed in the lateral plate mesoderm, signals through Alk8 to induce endodermal cells to become liver. When Bmp2b was overexpressed, medially located endodermal cells, fated to become pancreas and intestine, contributed to the liver. These data provide in vivo evidence for the existence of bipotential hepatopancreatic progenitors, and indicate that their fate is regulated by the medio-lateral patterning of the endodermal sheet, a process controlled by Bmp2b.
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