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Temperature-Induced uncoupling of cell cycle regulators
Developmental Biology ( IF 2.5 ) Pub Date : 2020-12-03 , DOI: 10.1016/j.ydbio.2020.11.010
Hanieh Falahati 1 , Woonyung Hur 2 , Stefano Di Talia 2 , Eric Wieschaus 3
Affiliation  

The early stages of development involve complex sequences of morphological changes that are both reproducible from embryo to embryo and often robust to environmental variability. To investigate the relationship between reproducibility and robustness we examined cell cycle progression in early Drosophila embryos at different temperatures. Our experiments show that while the subdivision of cell cycle steps is conserved across a wide range of temperatures (5–35 °C), the relative duration of individual steps varies with temperature. We find that the transition into prometaphase is delayed at lower temperatures relative to other cell cycle events, arguing that it has a different mechanism of regulation. Using an in vivo biosensor, we quantified the ratio of activities of the major mitotic kinase, Cdk1 and one of the major mitotic phosphatases PP1. Comparing activation profile with cell cycle transition times at different temperatures indicates that in early fly embryos activation of Cdk1 drives entry into prometaphase but is not required for earlier cell cycle events. In fact, chromosome condensation can still occur when Cdk1 activity is inhibited pharmacologically. These results demonstrate that different kinases are rate-limiting for different steps of mitosis, arguing that robust inter-regulation may be needed for rapid and ordered mitosis.



中文翻译:

细胞周期调节剂的温度诱导解偶联

发育的早期阶段涉及复杂的形态变化序列,这些变化既可在胚胎间重现,又通常对环境变化具有鲁棒性。为了研究可重复性和稳健性之间的关系,我们检查了不同温度下早期果蝇胚胎的细胞周期进程。我们的实验表明,虽然细胞周期步骤的细分在很宽的温度范围内(5-35°C)是保守的,但各个步骤的相对持续时间随温度而变化。我们发现,相对于其他细胞周期事件,向前中期的转变在较低温度下延迟,认为它具有不同的调节机制。使用体内生物传感器,我们量化了主要有丝分裂激酶 Cdk1 和主要有丝分裂磷酸酶 PP1 之一的活性比率。将激活曲线与不同温度下的细胞周期过渡时间进行比较表明,在早期的苍蝇胚胎中,Cdk1 的激活驱动进入前中期,但早期的细胞周期事件不需要。事实上,当药物抑制 Cdk1 活性时,仍然会发生染色体凝聚。这些结果表明,不同的激酶对有丝分裂的不同步骤具有限速作用,认为快速有序的有丝分裂可能需要强有力的相互调节。

更新日期:2020-12-03
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