Electrochemical Signaling in Development and Disease, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin-Buch, 13125, Germany.
Department of Clinical Pharmacology and Toxicology, Charité-Universitätsmedizin Berlin, Berlin, 10117, Germany.
Nat Commun. 2018 Jun 4;9(1):2161. doi: 10.1038/s41467-018-04566-1.
Development of a multiple-chambered heart from the linear heart tube is inherently linked to cardiac looping. Although many molecular factors regulating the process of cardiac chamber ballooning have been identified, the cellular mechanisms underlying the chamber formation remain unclear. Here, we demonstrate that cardiac chambers remodel by cell neighbour exchange of cardiomyocytes guided by the planar cell polarity (PCP) pathway triggered by two non-canonical Wnt ligands, Wnt5b and Wnt11. We find that PCP signalling coordinates the localisation of actomyosin activity, and thus the efficiency of cell neighbour exchange. On a tissue-scale, PCP signalling planar-polarises tissue tension by restricting the actomyosin contractility to the apical membranes of outflow tract cells. The tissue-scale polarisation of actomyosin contractility is required for cardiac looping that occurs concurrently with chamber ballooning. Taken together, our data reveal that instructive PCP signals couple cardiac chamber expansion with cardiac looping through the organ-scale polarisation of actomyosin-based tissue tension.
从线性心管发育成多腔心脏本质上与心脏成环有关。尽管已经鉴定出许多调节心脏腔球囊形成过程的分子因子，但腔形成的细胞机制仍不清楚。在这里，我们证明心肌细胞通过平面细胞极性（PCP）途径的细胞邻居交换来重塑心脏腔，该途径由两个非典型 Wnt 配体 Wnt5b 和 Wnt11 触发。我们发现 PCP 信号协调肌动球蛋白活性的定位，从而协调细胞邻居交换的效率。在组织尺度上，PCP 信号通过将肌动球蛋白收缩限制在流出道细胞的顶膜上来平面极化组织张力。肌动球蛋白收缩的组织尺度极化对于与腔球囊形成同时发生的心脏成环是必需的。总之，我们的数据表明，有指导意义的 PCP 信号通过基于肌动球蛋白的组织张力的器官尺度极化将心脏腔扩张与心脏成环偶联。
