BIOPHYSICS SEMINAR<br>Signal Integration and Cell Cycle Switches in Drosophila Embryonic Development</br>

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 Cdc25^twine 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 cdc25^string, 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.