Cell Size Determines the Strength of the Spindle Assembly Checkpoint during Embryonic Development

• Published in: Developmental cell Vol. 36; no. 3; pp. 344 - 352
• Main Authors: Galli, Matilde, Morgan, David O.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 08.02.2016
• Subjects: Animals; Caenorhabditis elegans - cytology; Caenorhabditis elegans - embryology; Caenorhabditis elegans - genetics; Cell Cycle Proteins - metabolism; Cell Size; Chromosome Segregation - physiology; Kinetochores - metabolism; M Phase Cell Cycle Checkpoints - genetics; Microtubules - metabolism; Spindle Apparatus - genetics
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2016.01.003

The spindle assembly checkpoint (SAC) delays mitotic progression when chromosomes are not properly attached to microtubules of the mitotic spindle. Cells vary widely in the extent to which they delay mitotic progression upon SAC activation. To explore the mechanisms that determine checkpoint strength in different cells, we systematically measured the mitotic delay induced by microtubule disruption at different stages of embryogenesis in Caenorhabditis elegans. Strikingly, we observed a gradual increase in SAC strength after each round of division. Analysis of mutants that alter cell size or ploidy revealed that SAC strength is determined primarily by cell size and the number of kinetochores. These findings provide clear evidence in vivo that the kinetochore-to-cytoplasm ratio determines the strength of the SAC, providing new insights into why cells exhibit such large variations in their SAC responses. [Display omitted] •In C. elegans embryos, small cells have a stronger spindle assembly checkpoint•Checkpoint strength increases in mutants with small cell size or increased ploidy•The amount of checkpoint-generating kinetochore signal is unaffected by cell size•Checkpoint strength is determined by the ratio of kinetochore signal to cytoplasm The spindle assembly checkpoint (SAC) delays mitotic progression when there are unattached kinetochores, but strength of the block varies between cell types. Galli and Morgan show that the kinetochore-to-cytoplasm ratio determines checkpoint strength. During C. elegans embryogenesis, SAC strength increases after each round of division due to decreasing cell size.