Self-Organized Nuclear Positioning Synchronizes the Cell Cycle in Drosophila Embryos

Abstract

The synchronous cleavage divisions of early embryogenesis require coordination of the cell-cycle oscillator, the dynamics of the cytoskeleton, and the cytoplasm. Yet, it remains unclear how spatially restricted biochemical signals are integrated with physical properties of the embryo to generate collective dynamics. Here, we show that synchronization of the cell cycle in Drosophila embryos requires accurate nuclear positioning, which is regulated by the cell-cycle oscillator through cortical contractility and cytoplasmic flows. We demonstrate that biochemical oscillations are initiated by local Cdk1 inactivation and spread through the activity of phosphatase PP1 to generate cortical myosin II gradients. These gradients cause cortical and cytoplasmic flows that control proper nuclear positioning. Perturbations of PP1 activity and optogenetic manipulations of cortical actomyosin disrupt nuclear spreading, resulting in loss of cell-cycle synchrony. We conclude that mitotic synchrony is established by a self-organized mechanism that integrates the cell-cycle oscillator and embryo mechanics.

Co-movement of astral microtubules, organelles and F-actin suggests aster positioning by surface forces in frog eggs

“…The high speed and predictability of the oscillatory movement on HOOK2-functionalized coverslips 220 enabled us to ask whether the cytosol was advected with the moving cytoplasmic networks. This question 221 was inspired by recent experiments showing that moving actomyosin gels advect cytosol in Drosophila 222 embryos (Deneke et al, 2019). We functionalized artificial MTOCs with caged fluorescein, linked to the 223 MTOCs via the caging group ( Fig 5A).…”

Plk4 triggers autonomous de novo centriole biogenesis and maturation

“…1, insets). Given that unfertilised eggs are not progressing through the cell cycle (Horner et al, 2006; Vardy and Orr-Weaver, 2007; Deneke et al, 2019), our findings suggest that centriole de novo formation, maturation and duplication can occur even without cell cycle transitions, in particular without having to undergo mitosis. Surprisingly, we also observed that the duplication time is similar for the first centrosomes assembled de novo at high (undiluted) and lower (diluted) concentration of Plk4 (Suppl.…”

“…It was previously proposed that in both human cells (La Terra et al, 2005; Lambrus et al, 2015) and Drosophila eggs (Rodrigues-Martins et al, 2007), centrioles that form de novo can then duplicate in a canonical fashion. However, this was never confirmed directly and raises some questions; since centriole duplication is thought to depend on centriole maturation, a process called centriole-to-centrosome conversion (Wang et al, 2011; Izquierdo et al, 2014; Fu et al, 2016; Chang et al, 2016) and known to be coupled to cell cycle progression, which does not occur in eggs (Horner et al, 2006; Vardy and Orr-Weaver, 2007; Deneke et al, 2019). Thus, we first asked whether de novo formed centrioles can recruit Ana1 and Asterless (Asl), required for centriole-to-centrosome conversion, followed by the recruitment of Plk4 and bona fide centriole duplication (Fig.…”

Simultaneous Regulation of Cytokinetic Furrow and Nucleus Positions by Cortical Tension Contributes to Proper DNA Segregation during Late Mitosis

“…Remarkably, it was recently shown that regulation of myosin II activity is critical for proper nuclear movement during the cleavage divisions of Drosophila embryos. This effect of myosin also involves the regulation of cortical contractility and the appearance of cytoplasmic flows [25]. Finally, a supplementary and redundant mechanism based on nuclear/microtubule interactions also drives nuclear displacement -probably through the pulling of the nucleus by microtubules.…”