Int. J. Dev. Biol. 58: 767 - 774 (2014)
doi: 10.1387/ijdb.140101jk
© UPV/EHU Press

Control of timing of embryonic M-phase entry and exit is differentially sensitive to CDK1 and PP2A balance

Mohammed El Dika1,2, Damian Dudka1,2, Claude Prigent1,2, Jean-Pierre Tassan1,2, Malgorzata Kloc3 and Jacek Z. Kubiak*,1,2

1CNRS, UMR 6290, Institute of Genetics and Development of Rennes, Cell Cycle Group, Rennes, France, 2University Rennes 1, UEB, IFR 140, Faculty of Medicine, Rennes, France and 3The Houston Methodist Research Institute, Houston, TX, USA

ABSTRACT Harmonious embryo development requires precise coordination between the timing of the cell cycle and the developmental program. Cyclin accumulation determines the timing of the cell cycle M-phase entry and its degradation determines the timing of the M-phase exit. It is well known that CDK1 and PP2A also govern M-phase entry. However, it is unknown how this kinase and phosphatase regulate the precise timing of events at the beginning of the M-phase and how they cooperate with cyclin metabolism. Here we use Xenopus laevis one-cell embryo cell-free extract experiments to answer this question critical for understanding the regulation of embryo development. Using, separately, low concentrations of the chemical inhibitor of CDK1, RO3306 (RO), or the inhibitor of phosphatases, okadaic acid (OA), we show that moderately diminished CDK1 or PP2A activities results in a delay and an acceleration respectively, of M-phase entry. Simultaneous diminution of CDK1 and PP2A activities results in an intermediate timing of M-phase entry, prolongs the duration of M-phase and diminishes the dynamics of cyclin B2 degradation. We thus show, for the first time, that equilibrium between CDK1 and PP2A specifies the timing of M-phase entry and exit and regulates the dynamics of cyclin B degradation upon M-phase exit in Xenopus laevis first embryonic mitosis.

Keywords:

cell cycle, cyclin, PP2A, CDK, M-phase entry

*Corresponding author e-mail: jacek.kubiak@univ-rennes1.fr