Quantitative Analysis of 3D Tissue Deformation Reveals Key Cellular Mechanism Associated with Initial Heart Looping
Quantitative Analysis of 3D Tissue Deformation Reveals Key Cellular Mechanism Associated with Initial Heart Looping
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DOI：
10.1016/j.celrep.2020.02.071
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发表时间：
2020-03-17
期刊：
影响因子：
8.8
通讯作者：
Morishita, Yoshihiro
中科院分区：
文献类型：
--
作者：
Kawahira, Naofumi;Ohtsuka, Daisuke;Morishita, Yoshihiro
尽管进行了广泛的研究，心脏循环的形态发生机制仍然存在争议，因为缺乏有关精确的组织水平的变形和组织和细胞动力学之间的定量关系的信息，这种信息的缺乏导致在评估以前提出的模型的困难。为了克服这些局限性，我们进行四维（4D）高分辨率成像，以重建组织变形图，这表明，在组织尺度上，初始心脏循环是通过左-右（LR）不对称的变形方向内的心肌管。我们进一步确定了右心肌中的F-肌动蛋白依赖性定向细胞重排是LR不对称组织变形的主要贡献者。我们的研究结果表明，心脏循环涉及动态和内在的细胞行为内的管状组织，并提供了一个显着不同的观点，从目前的模型是基于LR不对称的增长和/或应力管边界。最后，我们提出了一个最低限度的充分模型，也支持机械模拟的初始心脏循环。
Despite extensive study, the morphogenetic mechanisms of heart looping remain controversial because of a lack of information concerning precise tissue-level deformation and the quantitative relationship between tissue and cellular dynamics; this lack of information causes difficulties in evaluating previously proposed models. To overcome these limitations, we perform four-dimensional (4D) high-resolution imaging to reconstruct a tissue deformation map, which reveals that, at the tissue scale, initial heart looping is achieved by left-right (LR) asymmetry in the direction of deformation within the myocardial tube. We further identify F-actin-dependent directional cell rearrangement in the right myocardium as a major contributor to LR asymmetric tissue deformation. Our findings demonstrate that heart looping involves dynamic and intrinsic cellular behaviors within the tubular tissue and provide a significantly different viewpoint from current models that are based on LR asymmetry of growth and/or stress at the tube boundaries. Finally, we propose a minimally sufficient model for initial heart looping that is also supported by mechanical simulations.