Self-Organized Nuclear Positioning Synchronizes the Cell Cycle in Drosophila Embryos
Self-Organized Nuclear Positioning Synchronizes the Cell Cycle in Drosophila Embryos
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DOI：
10.1016/j.cell.2019.03.007
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发表时间：
2019-05-02
期刊：
影响因子：
64.5
通讯作者：
Di Talia, Stefano
中科院分区：
文献类型：
--
作者：
Deneke, Victoria E.;Puliafito, Alberto;Di Talia, Stefano
早期胚胎发生的同步卵裂分裂需要细胞周期振荡器、细胞骨架动力学和细胞质的协调。然而，目前尚不清楚空间限制的生化信号如何与胚胎的物理特性相结合，以产生集体动力学。在这里，我们发现果蝇胚胎细胞周期的同步需要精确的核定位，这是由细胞周期振荡器通过皮质收缩性和细胞质流动来调节的。我们证明生化振荡是由局部Cdkl失活引发的，并通过磷酸酶PP1的活性传播，产生皮质肌球蛋白II梯度。这些梯度引起皮层和细胞质流动，控制核的正确定位。PP1活性的扰动和皮质肌动球蛋白的光操纵破坏核扩散，导致细胞周期同步性的丧失。我们认为有丝分裂同步性是由细胞周期振荡器和胚胎力学相结合的自组织机制建立的。
The synchronous cleavage divisions of early embryogenesis require coordination of the cell-cycle oscillator, the dynamics of the cytoskeleton, and the cytoplasm. Yet, it remains unclear how spatially restricted biochemical signals are integrated with physical properties of the embryo to generate collective dynamics. Here, we show that synchronization of the cell cycle in Drosophila embryos requires accurate nuclear positioning, which is regulated by the cell-cycle oscillator through cortical contractility and cytoplasmic flows. We demonstrate that biochemical oscillations are initiated by local Cdkl inactivation and spread through the activity of phosphatase PP1 to generate cortical myosin II gradients. These gradients cause cortical and cytoplasmic flows that control proper nuclear positioning. Perturbations of PP1 activity and optogenctic manipulations of cortical actomyosin disrupt nuclear spreading, resulting in loss of cell-cycle synchrony. We conclude that mitotic synchrony is established by a self-organized mechanism that integrates the cell-cycle oscillator and embryo mechanics.