A homeostatic clock sets daughter centriole size in flies

Abstract

Centrioles are highly structured organelles of consistent size across cell types. Aydogan et al. show that, in early Drosophila embryos, Plk4 functions as a homeostatic clock, establishing an inverse relationship between growth rate and period to ensure that daughter centrioles grow to the correct size.

Feedback loops in the Plk4–STIL–HsSAS6 network coordinate site selection for procentriole formation

“…Recent work on Drosophila embryos has precisely described the dynamics of centriolar proteins, including Plk4 and Sas6 (Aydogan et al, 2018(Aydogan et al, , 2019. The time course of Drosophila Plk4 is similar to that indicated by this study, although the cell cycle is much shorter (~10-20 min) and the onset of centriolar Sas6 accumulation occurs before Plk4 reaches its peak (Aydogan et al, 2018(Aydogan et al, , 2019.…”

“…However, given that Plk4 appears as a ring only in late mitosis, when Sas6 begins to be recruited to centrioles, similar regulation to that indicated in our study may be occurring at the onset of centriole duplication. In line with this, there seems to be a small Plk4 peak around mitotic exit in Drosophila embryos (Aydogan et al, 2018(Aydogan et al, , 2019. Despite the homology, the precise mechanisms regulating the rate and timing of each process may differ depending on the cell, tissue type, and species.…”

“…However, given the limited number of copies of endogenous centriole duplication components (Bauer et al, 2016), the signal from an endogenous fluorescent tag could be too weak to detect in live imaging. To address this issue, as previously demonstrated in both Drosophila embryos (Aydogan et al, 2018(Aydogan et al, , 2019 and cultured human cells (Takao et al, 2018), we successfully used spinning disc confocal microscopy with an EMCCD camera to track the dynamics of endogenous proteins at centrioles. This avoided significant photobleaching of the fluorescent tag and phototoxicity to the cells throughout the entire cell cycle.…”

“…Recent work on Drosophila embryos has precisely described the dynamics of centriolar proteins, including Plk4 and Sas6 (Aydogan et al, 2018(Aydogan et al, , 2019. The time course of Drosophila Plk4 is similar to that indicated by this study, although the cell cycle is much shorter (~10-20 min) and the onset of centriolar Sas6 accumulation occurs before Plk4 reaches its peak (Aydogan et al, 2018(Aydogan et al, , 2019. However, given that Plk4 appears as a ring only in late mitosis, when Sas6 begins to be recruited to centrioles, similar regulation to that indicated in our study may be occurring at the onset of centriole duplication.…”

“…To achieve a fundamental understanding of centriole duplication processes, however, the dynamics of the components (e.g., timing, correlation, and the interdependency of centriolar accumulation) needs to be more precisely analyzed. While live imaging has been successfully used to visualize the dynamics of these components at centrioles throughout the entire cell cycle in Drosophila (Aydogan et al, 2018(Aydogan et al, , 2019 and Caenorhabditis elegans (Dammermann et al, 2008) embryos, gaining insight into these dynamic processes in human cells has remained challenging. In this study, we use optimized live imaging throughout the entire cell cycle in cultured human cells to precisely analyze and describe the dynamics of endogenous proteins participating in centriole duplication.…”