The Chiral Looping of the Embryonic Heart Is Formed by the Combination of Three Axial Asymmetries
The Chiral Looping of the Embryonic Heart Is Formed by the Combination of Three Axial Asymmetries
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DOI：
10.1016/j.bpj.2019.11.3397
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发表时间：
2020-02-04
影响因子：
3.4
通讯作者：
Fujimori, Toshihiko
中科院分区：
文献类型：
--
作者：
Honda, Hisao;Abe, Takaya;Fujimori, Toshihiko
在哺乳动物和鸟类中，心脏的胚胎发育包括将直管结构转换为三维螺旋环，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的形成机制，重点研究了螺旋环的左右利手的确定。在几何术语中，手性是三维空间中三个轴不对称的组合的结果。我们假设轴不对称与形态发生(弯曲和移位)之间的对应关系：初始心脏直管腹侧弯曲的背腹不对称和左右、前后不对称，心脏管向右移位导致的左右不对称，仅限于心脏管的前部。胚胎心脏手性环的形态发生是多细胞系统中的一个大尺度事件，在这个多细胞系统中，有相当大的物理力动态地运行。使用基于细胞的物理机械模型的计算机模拟和小鼠胚胎的实验，我们证实了这一假设。我们的结论是，管子的向右位移决定了回路的左旋螺杆。螺旋环的形成过程包括三个步骤：1)涉及结节相关信号的左右偏置系统，导致胚胎体的左右不对称；2)管子向右移位；最后3)左手螺旋环路。步骤1已经建立。我们的研究阐明了步骤3，强调了澄清步骤2的必要性；即，我们探索胚胎体内的左右不对称如何导致心管向右移位。
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.