Laboratoire de Physique des Lasers, Atomes, et Molécules, CNRS, UMR8523, Université Lille 1 Sciences et Technologies, Villeneuve d'Ascq, France.
PLoS Comput Biol. 2012 Jan;8(1):e1002329. doi: 10.1371/journal.pcbi.1002329. Epub 2012 Jan 5.
Maturation of vertebrate oocytes into haploid gametes relies on two consecutive meioses without intervening DNA replication. The temporal sequence of cellular transitions driving eggs from G2 arrest to meiosis I (MI) and then to meiosis II (MII) is controlled by the interplay between cyclin-dependent and mitogen-activated protein kinases. In this paper, we propose a dynamical model of the molecular network that orchestrates maturation of Xenopus laevis oocytes. Our model reproduces the core features of maturation progression, including the characteristic non-monotonous time course of cyclin-Cdks, and unveils the network design principles underlying a precise sequence of meiotic decisions, as captured by bifurcation and sensitivity analyses. Firstly, a coherent and sharp meiotic resumption is triggered by the concerted action of positive feedback loops post-translationally activating cyclin-Cdks. Secondly, meiotic transition is driven by the dynamic antagonism between positive and negative feedback loops controlling cyclin turnover. Our findings reveal a highly modular network in which the coordination of distinct regulatory schemes ensures both reliable and flexible cell-cycle decisions.
脊椎动物卵母细胞成熟为单倍体配子依赖于两次连续的减数分裂，而没有中间的 DNA 复制。驱动卵子从 G2 阻滞进入第一次减数分裂（MI），然后进入第二次减数分裂（MII）的细胞转变的时间顺序，是由细胞周期蛋白依赖性激酶和有丝分裂原激活蛋白激酶的相互作用所控制的。在本文中，我们提出了一个协调非洲爪蟾卵母细胞成熟的分子网络的动力学模型。我们的模型再现了成熟进程的核心特征，包括 cyclin-Cdks 的特征非单调时间历程，并通过分岔和敏感性分析揭示了精确的减数分裂决策序列背后的网络设计原则。首先，通过翻译后激活 cyclin-Cdks 的正反馈环的协同作用，触发了一致而尖锐的减数恢复。其次，由控制 cyclin 周转的正负反馈环之间的动态拮抗作用驱动减数转变。我们的研究结果揭示了一个高度模块化的网络，其中不同调节方案的协调确保了可靠和灵活的细胞周期决策。
