title: A dynamical model of oocyte maturation unveils precisely orchestrated meiotic decisions.
abstract: 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.
authors.affiliation: Laboratoire de Physique des Lasers, Atomes, et Molécules, CNRS, UMR8523, Université Lille 1 Sciences et Technologies, Villeneuve d'Ascq, France. benjamin.pfeuty@phlam.univ-lille1.fr
authors.forename: Benjamin
authors.initials: B
authors.lastname: Pfeuty
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Bodart
authors.forename: Ralf
authors.initials: R
authors.lastname: Blossey
authors.forename: Marc
authors.initials: M
authors.lastname: Lefranc
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D025461:Feedback, Physiological / Q000502:physiology; D008540:Meiosis / Q000502:physiology*; D008954:Models, Biological; D009865:Oocytes / Q000254:growth & development / Q000502:physiology*; D009866:Oogenesis / Q000502:physiology*; D010641:Phenotype; D015398:Signal Transduction / Q000502:physiology; D014982:Xenopus laevis
chemical_list: D018844:Cyclin-Dependent Kinases