Active torque generation by the actomyosin cell cortex drives left-right symmetry breaking.
Active torque generation by the actomyosin cell cortex drives left-right symmetry breaking.
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DOI：
10.7554/elife.04165
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发表时间：
2014-12-17
期刊：
影响因子：
7.7
通讯作者：
Grill SW
中科院分区：
文献类型：
--
作者：
Naganathan SR;Fürthauer S;Nishikawa M;Jülicher F;Grill SW
许多发育过程打破了左右（LR）对称性并导致了一致的惯用手。 LR 不对称性出现在发育早期，在许多物种中，这种不对称性的主要决定因素与细胞骨架有关。然而，潜在的手性不对称细胞骨架过程的本质仍然难以捉摸。在本研究中，我们将薄膜活性手性流体理论与线虫胚胎的实验分析相结合，表明肌动球蛋白皮层产生活性手性扭矩以促进手性对称性破缺。主动扭矩驱动受精卵中的手性反向旋转皮质流，取决于肌球蛋白活性，并且可以通过 Rho 信号传导的轻微变化来改变。值得注意的是，他们还在 4 细胞阶段执行手性偏斜事件，以建立线虫 LR 体轴。总而言之，我们的结果揭示了肌动球蛋白细胞骨架的一种新颖的大规模物理活性，为发育中的手性形态发生提供了基本机制。 DOI：http://dx.doi.org/10.7554/eLife.04165.001 大多数生物的左侧和右侧并不相同。这种“左右不对称”的一个众所周知的例子是人体心脏在人体中的位置。虽然人的心脏总是在左侧，但在其他情况下，可能会偏爱左侧或右侧：例如，有些人喜欢用右手写字，而另一些人则喜欢用左手写字。在动物中，左右不对称在胚胎发育的早期就开始了。已知细胞中一种称为细胞骨架的结构是造成许多物种不对称的原因。细胞骨架主要由两种类型的蛋白质组成——称为微管的杆状蛋白质和称为肌动蛋白的丝状蛋白质——但尚不清楚它如何参与建立左右不对称性。细胞骨架在细胞中具有许多功能：例如，它维持细胞的形状，在细胞分裂期间分裂细胞的内容物，以及在细胞内运输各种物质。细胞骨架不断移动和改变形状：所有这些活动都涉及另一种称为肌球蛋白的蛋白质，它与肌动蛋白丝结合并沿着肌动蛋白丝移动以产生拉力。纳加纳坦等人。研究了线虫新受精的秀丽隐杆线虫胚胎，当时它们只含有一个细胞。实验表明，肌球蛋白可以产生扭转力，扭转肌动蛋白皮质层，导致细胞骨架局部旋转，从而使细胞不对称。这是由一组称为 Rho 蛋白的蛋白质控制的。接下来，Naganathan 等人。研究了包含四个细胞的胚胎。同样，肌球蛋白在细胞骨架中产生局部旋转，这涉及在这个发育阶段建立左右身体方向。这些实验表明，单个细胞的细胞骨架的变化可以导致整个胚胎的不对称性。下一个挑战将是了解如何控制肌球蛋白，以便仅在特定细胞分裂期间发生旋转。 DOI：http://dx.doi.org/10.7554/eLife.04165.002
Many developmental processes break left–right (LR) symmetry with a consistent handedness. LR asymmetry emerges early in development, and in many species the primary determinant of this asymmetry has been linked to the cytoskeleton. However, the nature of the underlying chirally asymmetric cytoskeletal processes has remained elusive. In this study, we combine thin-film active chiral fluid theory with experimental analysis of the C. elegans embryo to show that the actomyosin cortex generates active chiral torques to facilitate chiral symmetry breaking. Active torques drive chiral counter-rotating cortical flow in the zygote, depend on myosin activity, and can be altered through mild changes in Rho signaling. Notably, they also execute the chiral skew event at the 4-cell stage to establish the C. elegans LR body axis. Taken together, our results uncover a novel, large-scale physical activity of the actomyosin cytoskeleton that provides a fundamental mechanism for chiral morphogenesis in development. DOI: http://dx.doi.org/10.7554/eLife.04165.001 Most living things have left and right sides that are not identical. A well-known example of this ‘left–right asymmetry’ is the position of the human heart within the human body. While the human heart is always on the left, in other situations it is possible for either the left side or the right side to be preferred: for example, some people prefer to write with their right hand, while others prefer to write with their left hand. In animals, left–right asymmetry starts early in the development of the embryo. A structure in cells called the cytoskeleton is known to be responsible for generating the asymmetry in many species. The cytoskeleton is mostly made of two types of proteins—rod-like proteins called microtubules and filaments of a protein called actin—but it is not clear how it is involved in establishing left–right asymmetry. The cytoskeleton has many functions in the cell: for example, it maintains the shape of the cell, it splits the contents of the cell during cell division, and it transports various things around inside the cell. The cytoskeleton is constantly moving and changing shape: all this activity involves another protein called myosin that binds to the actin filaments and moves along them to generate pulling forces. Naganathan et al. studied newly fertilized embryos of the nematode worm Caenorhabditis elegans when they contained just one cell. The experiments showed that myosin can generate turning forces that twist the actin cortical layer, leading to local rotations in the cytoskeleton that make the cell asymmetrical. This is controlled by a group of proteins called Rho proteins. Next, Naganathan et al. studied embryos that contained four cells. Again, myosin generates local rotations in the cytoskeleton, which are involved in setting up left–right body direction in this stage of development. These experiments show that changes in the cytoskeleton of individual cells can drive asymmetry in the whole embryo. The next challenge will be to understand how myosin is controlled so that rotations only occur during specific cell divisions. DOI: http://dx.doi.org/10.7554/eLife.04165.002