The primary cilium coordinates early cardiogenesis and hedgehog signaling in cardiomyocyte differentiation
The primary cilium coordinates early cardiogenesis and hedgehog signaling in cardiomyocyte differentiation
复制标题
DOI：
10.1242/jcs.049676
复制
发表时间：
2009-09-01
影响因子：
4
通讯作者：
Christensen, Soren T.
中科院分区：
文献类型：
--
作者：
Clement, Christian A.;Kristensen, Stine G.;Christensen, Soren T.
初级纤毛（感觉细胞器）的组装或功能缺陷与哺乳动物的发育缺陷和疾病密切相关。在这里，我们研究了初级纤毛在调节刺猬信号和早期心脏发生中的功能。我们报道，多能 P19.CL6 小鼠干细胞系可以分化为跳动的心肌细胞，形成初级纤毛，其中含有刺猬通路的重要成分，包括 Smoothened、Patched-1 和 Gli2。通过 Ift88 和 Ift20 siRNA 敲低初级纤毛或用 Smoothened 抑制剂环杷明处理，可阻断 P19.CL6 细胞中的刺猬信号传导，以及细胞分化为跳动的心肌细胞。 Ift88(tm1Rpw)（Ift88-null）小鼠的 E11.5 胚胎不形成纤毛，具有心室扩张、心肌小梁减少和流出道发育异常。这些数据支持这样的结论：心脏初级纤毛在早期心脏发育中至关重要，它们在一定程度上协调刺猬信号传导。
Defects in the assembly or function of primary cilia, which are sensory organelles, are tightly coupled to developmental defects and diseases in mammals. Here, we investigated the function of the primary cilium in regulating hedgehog signaling and early cardiogenesis. We report that the pluripotent P19.CL6 mouse stem cell line, which can differentiate into beating cardiomyocytes, forms primary cilia that contain essential components of the hedgehog pathway, including Smoothened, Patched-1 and Gli2. Knockdown of the primary cilium by Ift88 and Ift20 siRNA or treatment with cyclopamine, an inhibitor of Smoothened, blocks hedgehog signaling in P19.CL6 cells, as well as differentiation of the cells into beating cardiomyocytes. E11.5 embryos of the Ift88(tm1Rpw) (Ift88-null) mice, which form no cilia, have ventricular dilation, decreased myocardial trabeculation and abnormal outflow tract development. These data support the conclusion that cardiac primary cilia are crucial in early heart development, where they partly coordinate hedgehog signaling.