Short-Term Integration of Cdc25 Dynamics Controls Mitotic Entry during Drosophila Gastrulation

摘要

Cells commit to mitosis by abruptly activating the mitotic cyclin-Cdk complexes. During Drosophila gastrulation, mitosis is associated with the transcriptional activation of cdc25 string, a phosphatase that activates Cdk1. Here, we demonstrate that the switch-like entry into mitosis observed in the Drosophila embryo during the 14 th mitotic cycle is timed by the dynamics of Cdc25 string accumulation. The switch operates as a short-term integrator, a property that can improve the reliable control of timing of mitosis. The switch is independent of the positive feedback between Cdk1 and Cdc25 string and of the double negative feedback between Cdk1 and Wee1. We propose that the properties of the mitotic switch are established by the out-of-equilibrium properties of the covalent modification cycle controlling Cdk1 activity. Such covalent modification cycles, triggered by transcriptional expression of the activating enzymes, might be a widespread strategy to obtain reliable and switch-like control of cell decisions. Drosophila embryos control switch-like entry into mitosis by measuring Cdc25 levels. Di Talia and Wieschaus show that this mechanism is not dependent on feedback. Instead, the fly blastoderm exploits pre-equilibrium Cdc25 dynamics and short-term averaging of Cdc25 concentrations to achieve a more precisely regulated ultrasensitive switch.