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Asymmetric division through a reduction of microtubule centering forces

机译:通过减少微管对中力来实现不对称分裂

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摘要

Asymmetric divisions are essential for the generation of cell fate and size diversity. They implicate cortical domains where minus end–directed motors, such as dynein, are activated to pull on microtubules to decenter asters attached to centrosomes, nuclei, or spindles. In asymmetrically dividing cells, aster decentration typically follows a centering phase, suggesting a time-dependent regulation in the competition between microtubule centering and decentering forces. Using symmetrically dividing sea urchin zygotes, we generated cortical domains of magnetic particles that spontaneously cluster endogenous dynein activity. These domains efficiently attract asters and nuclei, yielding marked asymmetric divisions. Remarkably, aster decentration only occurred after asters had first reached the cell center. Using intracellular force measurement and models, we demonstrate that this time-regulated imbalance results from a global reduction of centering forces rather than a local maturation of dynein activity at the domain. Those findings define a novel paradigm for the regulation of division asymmetry.
机译:非对称分裂对于细胞命运和大小多样性的产生至关重要。它们牵涉到皮质区域,在其中激活了负向导向马达(例如达因)的微管区拉动微管,使附着在中心体,核或纺锤体上的紫偏心。在不对称分裂的细胞中,紫苑偏心通常遵循定心阶段,这表明微管定心和偏心力之间的竞争具有时间依赖性。使用对称划分的海胆受精卵,我们生成了磁性颗粒的皮层结构域,这些结构域自发地聚集了内源性动力蛋白。这些结构域有效地吸引了星号和原子核,产生了明显的不对称分裂。值得注意的是,紫苑偏心仅在紫苑首次到达细胞中心后才发生。使用细胞内力测量和模型,我们证明了这种时间调节的失衡是由于集中力的整体降低而不是域中动力蛋白活性的局部成熟所致。这些发现为分割不对称的调节定义了一种新颖的范例。

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