title: Waves of Cdk1 Activity in S Phase Synchronize the Cell Cycle in Drosophila Embryos.
abstract: Embryos of most metazoans undergo rapid and synchronous cell cycles following fertilization. While diffusion is too slow for synchronization of mitosis across large spatial scales, waves of Cdk1 activity represent a possible process of synchronization. However, the mechanisms regulating Cdk1 waves during embryonic development remain poorly understood. Using biosensors of Cdk1 and Chk1 activities, we dissect the regulation of Cdk1 waves in the Drosophila syncytial blastoderm. We show that Cdk1 waves are not controlled by the mitotic switch but by a double-negative feedback between Cdk1 and Chk1. Using mathematical modeling and surgical ligations, we demonstrate a fundamental distinction between S phase Cdk1 waves, which propagate as active trigger waves in an excitable medium, and mitotic Cdk1 waves, which propagate as passive phase waves. Our findings show that in Drosophila embryos, Cdk1 positive feedback serves primarily to ensure the rapid onset of mitosis, while wave propagation is regulated by S phase events.
authors.affiliation: Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Victoria E
authors.initials: VE
authors.lastname: Deneke
authors.affiliation: Department of Physics, University of California San Diego, La Jolla, CA 92093, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Melbinger
authors.affiliation: Department of Physics, University of California San Diego, La Jolla, CA 92093, USA.
authors.forename: Massimo
authors.initials: M
authors.lastname: Vergassola
authors.affiliation: Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA. Electronic address: stefano.ditalia@duke.edu.
authors.forename: Stefano
authors.initials: S
authors.lastname: Di Talia
mesh_terms: D000818:Animals; D001756:Blastoderm / Q000196:embryology; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D000071877:Checkpoint Kinase 1 / Q000378:metabolism*; D004330:Drosophila / Q000196:embryology*; D029721:Drosophila Proteins / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000378:metabolism; D047108:Embryonic Development / Q000502:physiology; D004789:Enzyme Activation / Q000235:genetics; D008938:Mitosis / Q000502:physiology*; D008962:Models, Theoretical; D016196:S Phase / Q000502:physiology*
chemical_list: D029721:Drosophila Proteins; D000071877:Checkpoint Kinase 1; C000605877:grp protein, Drosophila; D016203:CDC2 Protein Kinase; C000601753:Cdk1 protein, Drosophila