Manipulating the nature of embryonic mitotic waves.
Manipulating the nature of embryonic mitotic waves.
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DOI：
10.1016/j.cub.2022.10.014
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发表时间：
2022-11-21
期刊：
影响因子：
9.2
通讯作者：
Di Talia, Stefano
中科院分区：
文献类型：
--
作者：
Hayden, Luke;Hur, Woonyung;Vergassola, Massimo;Di Talia, Stefano
早期胚胎发生的特点是快速和同步的卵裂分裂，这往往是由Cdk 1活性的波形模式控制。有丝分裂波有两种机制：扫描波和触发波。这两种机制引起不同的波的速度，依赖于物理和分子参数，和空间分布的Cdk 1活动：向上扫描梯度与行波阵面。这两种机制都依赖于控制细胞周期的瞬时双稳态，并通过细胞周期进程的速度来区分：扫描/触发波分别针对快速/慢速驱动器出现。在这里，使用定量成像的Cdk 1活动和理论，我们说明，扫描波是果蝇胚胎的主导机制，并测试两个基本的预测从扫描到触发波的过渡。我们证明，扫描波可以变成触发波，如果细胞周期减慢遗传或如果显着延迟细胞周期进程中引入整个胚胎通过改变核密度。我们的遗传实验表明，波罗激酶是胚盘分裂的一个主要限速调节因子，降低其活性的遗传扰动可以诱导从扫描波到触发波的转变。此外，我们表明，温度的变化导致一个基本上均匀的间期和有丝分裂的放缓。这导致在宽的温度范围内观察到扫描波，尽管细胞周期持续时间显著不同。总的来说，我们的理论和实验相结合，阐明了果蝇胚胎发生中有丝分裂波的性质，它们的控制机制和它们之间的相互转换。Hayden等人表明果蝇胚胎中的有丝分裂波受Cdk 1活性的扫描波控制。这些波需要通过细胞周期快速和同步的进展，改变这些特征中的任何一个都会导致触发波而不是扫描波。温度不影响Cdk 1波的性质。
Early embryogenesis is characterized by rapid and synchronous cleavage divisions, which are often controlled by wave-like patterns of Cdk1 activity. Two mechanisms have been proposed for mitotic waves: sweep and trigger waves. The two mechanisms give rise to different wave speeds, dependencies on physical and molecular parameters, and spatial profiles of Cdk1 activity: upward sweeping gradients vs traveling wavefronts. Both mechanisms hinge on the transient bistability governing the cell cycle and are differentiated by the speed of the cell cycle progression: Sweep/trigger waves arise for rapid/slow drives, respectively. Here, using quantitative imaging of Cdk1 activity and theory, we illustrate that sweep waves are the dominant mechanism in Drosophila embryos, and test two fundamental predictions on the transition from sweep to trigger waves. We demonstrate that sweep waves can be turned into trigger waves if the cell cycle is slowed down genetically or if significant delays in the cell cycle progression are introduced across the embryo by altering nuclear density. Our genetic experiments demonstrate that Polo kinase is a major rate-limiting regulator of the blastoderm divisions and genetic perturbations reducing its activity can induce the transition from sweep to trigger waves. Furthermore, we show that changes in temperature cause an essentially uniform slowdown of interphase and mitosis. That results in sweep waves being observed across a wide temperature range despite the cell cycle durations being significantly different. Collectively, our combination of theory and experiments elucidates the nature of mitotic waves in Drosophila embryogenesis, their control mechanisms and their mutual transitions. Hayden et al. show that mitotic waves in Drosophila embryos are controlled by sweep waves of Cdk1 activity. These waves require fast and synchronous progression through the cell cycle and altering either of these features results in trigger rather than sweep waves. Temperature does not affect the properties of Cdk1 waves.
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