Browsing by Subject "Synchronization"

Early development in most metazoans is characterized by remarkably fast and coordinated cell cycles. Nonetheless, it is unclear what organizational principles underlie cell cycle synchronization across a large developing embryo. We found that cell cycle synchronization in Drosophila arises through the self-organized positioning of nuclei, which is regulated by the spatiotemporal dynamics of the cell cycle, cortical contractions, and cytoplasmic streaming. First, local Cdk1 downregulation at mitotic exit initiates the damped spreading of PP1 activity, which is responsible for recruiting myosin II to cortical regions that surround the nuclei, where gradients of contractility are generated. These gradients drive cortical and cytoplasmic flows that properly position the nuclei across the embryo. Uniform positioning of nuclei across the embryo is required for the emergence of synchronous cell cycles. Once at the surface of the embryo, nuclei undergo four metachronous cell cycles, which spread in a wave-like manner with remarkable speed across the large distance of the egg. Using a Cdk1 biosensor, we found that travelling waves of Cdk1 activity propagate through the embryo and synchronize the cell cycle during S-phase through an active mechanism, while mitotic events simply follow S-phase synchronization with a delay. Taken together, a self-organized mechanism that spreads nuclei uniformly is required early on in development to give rise to synchronous divisions. Cell cycle synchrony is then maintained by waves of Cdk1 activity, ensuring that all nuclei initiate the mid-blastula transition simultaneously. This work highlights the importance of chemical waves and cytoplasmic flows in the spatiotemporal regulation of the cell cycle of large embryos.