Calzone Laurence, Thieffry Denis, Tyson John J, Novak Bela
Molecular Network Dynamics Research Group of Hungarian Academy of Sciences and Budapest University of Technology and Economics, Budapest, Gellért tér, Hungary.
Mol Syst Biol. 2007;3:131. doi: 10.1038/msb4100171. Epub 2007 Jul 31.
Immediately following fertilization, the fruit fly embryo undergoes 13 rapid, synchronous, syncytial nuclear division cycles driven by maternal genes and proteins. During these mitotic cycles, there are barely detectable oscillations in the total level of B-type cyclins. In this paper, we propose a dynamical model for the molecular events underlying these early nuclear division cycles in Drosophila. The model distinguishes nuclear and cytoplasmic compartments of the embryo and permits exploration of a variety of rules for protein transport between the compartments. Numerical simulations reproduce the main features of wild-type mitotic cycles: patterns of protein accumulation and degradation, lengthening of later cycles, and arrest in interphase 14. The model is consistent with mutations that introduce subtle changes in the number of mitotic cycles before interphase arrest. Bifurcation analysis of the differential equations reveals the dependence of mitotic oscillations on cycle number, and how this dependence is altered by mutations. The model can be used to predict the phenotypes of novel mutations and effective ranges of the unmeasured rate constants and transport coefficients in the proposed mechanism.
受精后,果蝇胚胎立即经历由母体基因和蛋白质驱动的13个快速、同步的合胞体核分裂周期。在这些有丝分裂周期中,B型细胞周期蛋白的总量几乎没有可检测到的振荡。在本文中,我们提出了一个关于果蝇早期核分裂周期潜在分子事件的动力学模型。该模型区分了胚胎的核区室和细胞质区室,并允许探索区室间蛋白质转运的各种规则。数值模拟再现了野生型有丝分裂周期的主要特征:蛋白质积累和降解模式、后期周期的延长以及在间期14的停滞。该模型与在间期停滞前有丝分裂周期数量引入细微变化的突变一致。微分方程的分岔分析揭示了有丝分裂振荡对周期数的依赖性,以及这种依赖性如何因突变而改变。该模型可用于预测新突变的表型以及所提出机制中未测量的速率常数和转运系数的有效范围。