Zeng Xin-Xin I, Yelon Deborah
Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
Cell Rep. 2014 May 22;7(4):951-60. doi: 10.1016/j.celrep.2014.04.013. Epub 2014 May 9.
Heart assembly requires input from two populations of progenitor cells, the first and second heart fields (FHF and SHF), that differentiate at distinct times and create different cardiac components. The cardiac outflow tract (OFT) is built through recruitment of late-differentiating, SHF-derived cardiomyocytes to the arterial pole of the heart. The mechanisms responsible for selection of an appropriate number of OFT cells from the SHF remain unclear. Here, we find that cell adhesion molecule 4 (cadm4) is essential for restricting the size of the zebrafish OFT. Knockdown of cadm4 causes dramatic OFT expansion, and overexpression of cadm4 results in a greatly diminished OFT. Moreover, cadm4 activity limits the production of OFT progenitor cells and the duration of their accumulation at the arterial pole. Together, our data suggest a role for cell adhesion in restraining SHF deployment to the OFT, perturbation of which could cause congenital OFT defects.
心脏组装需要来自两组祖细胞的输入，即第一和第二心脏区域（FHF和SHF），它们在不同时间分化并产生不同的心脏组件。心脏流出道（OFT）是通过将晚期分化的、源自SHF的心肌细胞募集到心脏的动脉极而构建的。从SHF中选择适当数量的OFT细胞的机制仍不清楚。在这里，我们发现细胞粘附分子4（cadm4）对于限制斑马鱼OFT的大小至关重要。敲低cadm4会导致OFT显著扩张，而cadm4的过表达会导致OFT大大缩小。此外，cadm4活性限制了OFT祖细胞的产生及其在动脉极积累的持续时间。总之，我们的数据表明细胞粘附在限制SHF向OFT的部署中起作用，对此的扰动可能导致先天性OFT缺陷。
