Bloomekatz Joshua, Singh Reena, Prall Owen Wj, Dunn Ariel C, Vaughan Megan, Loo Chin-San, Harvey Richard P, Yelon Deborah
Division of Biological Sciences, University of California, San Diego, La Jolla, United States.
Victor Chang Cardiac Research Institute, Darlinghurst, Australia.
Elife. 2017 Jan 18;6:e21172. doi: 10.7554/eLife.21172.
Communication between neighboring tissues plays a central role in guiding organ morphogenesis. During heart tube assembly, interactions with the adjacent endoderm control the medial movement of cardiomyocytes, a process referred to as cardiac fusion. However, the molecular underpinnings of this endodermal-myocardial relationship remain unclear. Here, we show an essential role for platelet-derived growth factor receptor alpha (Pdgfra) in directing cardiac fusion. Mutation of disrupts heart tube assembly in both zebrafish and mouse. Timelapse analysis of individual cardiomyocyte trajectories reveals misdirected cells in zebrafish mutants, suggesting that PDGF signaling steers cardiomyocytes toward the midline during cardiac fusion. Intriguingly, the ligand is expressed in the endoderm medial to the -expressing myocardial precursors. Ectopic expression of interferes with cardiac fusion, consistent with an instructive role for PDGF signaling. Together, these data uncover a novel mechanism through which endodermal-myocardial communication can guide the cell movements that initiate cardiac morphogenesis.
相邻组织之间的通讯在引导器官形态发生过程中起着核心作用。在心脏管组装过程中,与相邻内胚层的相互作用控制着心肌细胞的向内侧移动,这一过程被称为心脏融合。然而,这种内胚层 - 心肌关系的分子基础仍不清楚。在这里,我们展示了血小板衍生生长因子受体α(Pdgfra)在指导心脏融合中的重要作用。斑马鱼和小鼠中该基因的突变都会破坏心脏管组装。对单个心肌细胞轨迹的延时分析揭示了斑马鱼突变体中细胞的错误定向,这表明血小板衍生生长因子(PDGF)信号在心脏融合过程中引导心肌细胞朝向中线。有趣的是,配体在内胚层中表达,该内胚层位于表达该基因的心肌前体的内侧。该基因的异位表达会干扰心脏融合,这与PDGF信号的指导作用一致。总之,这些数据揭示了一种新机制,通过该机制内胚层 - 心肌通讯可以引导启动心脏形态发生的细胞运动。