In mammals and birds, embryonic development of the heart involves conversion of a straight tubular structure into a three-dimensional helical loop, which is a chiral structure. We investigated theoretically the mechanism of helical loop formation of the mouse embryonic heart, especially focusing on determination of left-/right-handedness of the helical loop. In geometrical terms, chirality is the result of the combination of three axial asymmetries in three-dimensional space. We hypothesized the following correspondences between axial asymmetries and morphogenesis (bending and displacement): the dorsal-ventral asymmetry by ventral bending of a straight tube of the initial heart and the left-right and anterior-posterior asymmetries, the left-right asymmetry by rightward displacement of the heart tube, which is confined to the anterior region of the tube. Morphogenesis of chiral looping of the embryonic heart is a large-scaled event of the multicellular system in which substantial physical force operates dynamically. Using computer simulations with a cell-based physico-mechanical model and experiments with mouse embryos, we confirmed the hypothesis. We conclude that rightward displacement of the tube determines the left-handed screw of the loop. The process of helix loop formation consists of three steps: 1) the left-right biasing system involving Nodal-related signals that leads to left-right asymmetry in the embryonic body; 2) the rightward displacement of the tube; and finally 3) the left-handed helical looping. Step 1 is already established. Step 3 is elucidated by our study, which highlights the need for step 2 to be clarified; namely, we explore how the left-right asymmetry in the embryonic body leads to the rightward displacement of the heart tube.

中文翻译：

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胚胎心脏的手性环由三个轴不对称组合而成

在哺乳动物和鸟类中，心脏的胚胎发育涉及将直管结构转化为三维螺旋环，这是一种手性结构。我们从理论上研究了小鼠胚胎心脏螺旋环形成的机制，特别关注螺旋环的左手/右手性的确定。在几何学上，手性是三维空间中三个轴不对称组合的结果。我们假设轴不对称和形态发生（弯曲和位移）之间存在以下对应关系：由初始心脏直管腹侧弯曲引起的背腹不对称和左右和前后不对称，由向右引起的左右不对称心管移位，这仅限于管的前部区域。胚胎心脏手性环的形态发生是多细胞系统的一个大规模事件，其中大量的物理力动态运行。使用基于细胞的物理机械模型的计算机模拟和小鼠胚胎实验，我们证实了这一假设。我们得出结论，管子的向右位移决定了环的左旋螺钉。螺旋环形成的过程包括三个步骤：1）左右偏置系统，涉及节点相关信号，导致胚胎体内左右不对称；2）管子的右移；最后 3) 左手螺旋循环。第 1 步已经建立。我们的研究阐明了第 3 步，强调需要澄清第 2 步；即，