Diffusion through a liquid crystalline compartment regulates meiotic recombination

Abstract

Meiosis is the specialized form of cell division that produces haploid cells to enable sexual reproduction. Central to this process is recombination between homologous chromosomes, which gives rise to genetic diversity. Faithful meiotic chromosome segregation, and thus fertility, also depends on the formation of crossovers between each pair of chromosomes. The number and spacing of crossovers is tightly regulated, but the mechanisms that govern crossover patterning remain unclear. Previous work from our lab demonstrated that the synaptonemal complex (SC), a protein polymer that forms between homologous chromosomes during early meiosis, is a liquid crystal that arises through regulated phase separation. We are currently investigating the hypothesis that this medium might enable biochemical signals to diffuse along the interface between paired chromosomes to coordinate crossover patterning. We identified and characterized a family of four RING finger proteins (ZHP-1-4) in C. elegans that cooperate to promote and limit the number of crossovers during meiosis. Here, using in vivo imaging and fluorescence correlation spectroscopy (FCS), we show that ZHP-3 is mobile within the SC, even after accumulating at crossover sites. We corroborate this result by measuring fluorescence recovery after photobleaching (FRAP), and further show that this property of ZHP-3 is unique among several pro-crossover factors. Our results, together with the known interactions of ZHP-1-4, suggest that a reaction-diffusion system within the SC may pattern crossovers during meiosis.