Signal Integration and Cell Cycle Switches in Drosophila Embryonic Development
Embryonic development is characterized by rapid yet precise and reproducible cellular decisions. The molecular mechanisms ensuring that cellular decisions during development are both rapid and accurate remain poorly understood. I will describe our attempts to uncover these mechanisms by studying cell cycle control during early Drosophila embryonic development. In the first part of my talk, I will describe the identification of a novel switch-like mechanism controlling the cell cycle pause at the Mid-Blastula Transition (MBT, when zygotic transcription is initiated and maternal mRNAs are degraded). I will show that, contrary to current models, the decision to arrest the cell cycle at the MBT is not controlled by degradation of maternal mRNA of cdc25, but by a switch-like increase in the degradation rate of Cdc25twine protein. In the second part of my talk, I will describe the mechanism controlling the decision of cells to enter mitosis during gastrulation. Cells commit to mitosis by abruptly activating the mitotic cyclin-Cdk complexes. During Drosophila gastrulation, mitosis is associated with the transcriptional activation of cdc25string, a phosphatase that activates Cdk1. I will show that the switch controlling entry into mitosis operates as a short-term integrator, a property that can improve the reliable control of timing of mitosis. The switch is established by the out-of-equilibrium properties of the covalent modification cycle controlling Cdk1 activity and is independent of the positive feedback observed in other systems. I will discuss how short-term integration might be a widespread strategy to obtain reliable and switch-like control of cellular decisions.