Length-sensitive partitioning of Caenorhabditis elegans meiotic chromosomes senses proximity and number of crossover sites

Abstract Sensing and control of size is critical for cellular function and survival. A striking example of size sensing occurs during meiosis in the nematode Caenorhabditis elegans . C. elegans chromosomes compare the lengths of the two chromosome “arms” demarcated by the position of their single off-center crossover, and differentially modify these arms to ensure that sister chromatid cohesion is lost specifically on the shorter arm in the first meiotic division, while the longer arm maintains cohesion until the second division. While many of the downstream steps leading to cohesion loss have been characterized, the length sensing process itself remains poorly understood. Here, we have used cytological visualization of the short arm, combined with quantitative microscopy, live imaging, and simulations, to investigate the principles underlying length-sensitive chromosome partitioning. By quantitatively analyzing short arm designation patterns on fusion chromosomes carrying multiple crossovers, we develop a model in which a short arm-determining factor originates at crossover designation sites, diffuses within the phase-separated synaptonemal complex, and accumulates within crossover-bounded chromosome segments. We demonstrate experimental support for a critical assumption of this model, that crossovers act as boundaries to diffusion within the synaptonemal complex. Further, we develop a discrete simulation based on our results that recapitulates a wide variety of observed partitioning outcomes in both wild type and previously reported mutants. Our results suggest that the concentration of a diffusible factor is used as a proxy for chromosome length, enabling the correct designation of short and long arms and proper segregation of chromosomes.