A minimal mathematical model for polarity establishment and centralsplindlin-independent cytokinesis

bioRxiv Pub Date : 2024-08-09 DOI:10.1101/2024.08.07.607072
O. Maxian, Katrina M Longhini, M. Glotzer
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Abstract

The anterior-posterior axis of Caenorhabditis elegans embryos is determined by the position of sperm entry. The sperm-provided centrosome induces local inhibition of cortical contractility, leading to large-scale myosin flows. This process is driven by the guanine nucleotide exchange factor (GEF) ECT-2, which activates myosin through the GTPase RHO-1. Previously, we showed that in both cell polarization and cytokinesis, Aurora A (AIR-1) is activated on the centrosomes and diffuses to the cortex, where it locally inhibits ECT-2, leading to gradients in myosin concentration. These gradients in turn drive long-range flows that amplify ECT-2 asymmetries (Longhini and Glotzer, 2022). Here, we construct a mathematical model to test whether a minimal set of well characterized, essential elements are necessary and sufficient to explain the spatiotemporal dynamics of AIR-1, ECT-2, and myosin during polarization of the C. elegans model organism. We show that robust establishment of polarity can be obtained in response to a weak AIR-1 signal, and demonstrate the relevance of rapid ECT-2 exchange and a persistent AIR-1 cue during polarization. The tuned model also correctly predicts previously-observed ultrasensitive ECT-2 dynamics during cytokinesis, suggesting that the same minimal circuit operates in both processes.
极性建立和不依赖于中心纵轴的细胞分裂的最小数学模型
秀丽隐杆线虫胚胎的前后轴是由精子进入的位置决定的。精子提供的中心体诱导局部抑制皮层收缩,导致大规模肌球蛋白流动。这一过程由鸟嘌呤核苷酸交换因子(GEF)ECT-2 驱动,ECT-2 通过 GTP 酶 RHO-1 激活肌球蛋白。我们之前的研究表明,在细胞极化和细胞分裂过程中,极光 A(AIR-1)都会在中心体上被激活并扩散到皮层,在皮层局部抑制 ECT-2,从而导致肌球蛋白浓度梯度。这些梯度反过来又推动了长程流动,从而放大了 ECT-2 的不对称性(Longhini 和 Glotzer,2022 年)。在此,我们构建了一个数学模型,以检验在优雅类模式生物的极化过程中,是否有必要和有足够的必要元素来解释 AIR-1、ECT-2 和肌球蛋白的时空动态。我们的研究表明,极性的稳健建立可以对微弱的 AIR-1 信号做出反应,并证明了极化过程中快速的 ECT-2 交换和持续的 AIR-1 提示的相关性。调谐模型还正确预测了之前观察到的细胞分裂过程中超敏 ECT-2 的动态,这表明在这两个过程中运行的是相同的最小回路。
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