Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany.
Biotechnology Center, Technische Universität Dresden, 01307 Dresden, Germany.
Proc Natl Acad Sci U S A. 2021 May 18;118(20). doi: 10.1073/pnas.2021814118.
Proper left-right symmetry breaking is essential for animal development, and in many cases, this process is actomyosin-dependent. In embryos active torque generation in the actomyosin layer promotes left-right symmetry breaking by driving chiral counterrotating cortical flows. While both Formins and Myosins have been implicated in left-right symmetry breaking and both can rotate actin filaments in vitro, it remains unclear whether active torques in the actomyosin cortex are generated by Formins, Myosins, or both. We combined the strength of genetics with quantitative imaging and thin film, chiral active fluid theory to show that, while Non-Muscle Myosin II activity drives cortical actomyosin flows, it is permissive for chiral counterrotation and dispensable for chiral symmetry breaking of cortical flows. Instead, we find that CYK-1/Formin activation in RhoA foci is instructive for chiral counterrotation and promotes in-plane, active torque generation in the actomyosin cortex. Notably, we observe that artificially generated large active RhoA patches undergo rotations with consistent handedness in a CYK-1/Formin-dependent manner. Altogether, we conclude that CYK-1/Formin-dependent active torque generation facilitates chiral symmetry breaking of actomyosin flows and drives organismal left-right symmetry breaking in the nematode worm.
正确的左右对称破缺对于动物发育至关重要，在许多情况下，这个过程依赖于肌动球蛋白。在胚胎中，肌动球蛋白层中活性扭矩的产生通过驱动手性反向旋转皮层流促进左右对称破缺。尽管formin 和肌球蛋白都与左右对称破缺有关，并且两者都可以在体外旋转肌动蛋白丝，但活性肌动球蛋白皮层中的扭矩是否由formin、肌球蛋白或两者共同产生仍不清楚。我们将遗传学的优势与定量成像和薄膜、手性活性流体理论相结合，表明虽然非肌肉肌球蛋白 II 活性驱动皮层肌动球蛋白流，但它对手性反转是允许的，而对手性反转的皮层流是可有可无的。相反，我们发现 RhoA 焦点中的 CYK-1/formin 激活对手性反转具有指示性，并促进肌动球蛋白皮层中的平面活性扭矩产生。值得注意的是，我们观察到人工产生的大活性 RhoA 斑块以 CYK-1/formin 依赖的方式以一致的手性进行旋转。总之，我们得出结论，CYK-1/formin 依赖性活性扭矩产生有助于肌动球蛋白流的手性对称破缺，并驱动线虫蠕虫的生物体左右对称破缺。
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