The telomere bouquet is a hub where meiotic double-strand breaks, synapsis, and stable homolog juxtaposition are coordinated in the zebrafish, Danio rerio

Meiosis is a cellular program that generates haploid gametes for sexual reproduction. While chromosome events that contribute to reducing ploidy (homologous chromosome pairing, synapsis, and recombination) are well conserved, their execution varies across species and even between sexes of the same species. The telomere bouquet is a conserved feature of meiosis that was first described nearly a century ago, yet its role is still debated. Here we took advantage of the prominent telomere bouquet in zebrafish, Danio rerio, and super-resolution microscopy to show that axis morphogenesis, synapsis, and the formation of double-strand breaks (DSBs) all take place within the immediate vicinity of telomeres. We established a coherent timeline of events and tested the dependence of each event on the formation of Spo11-induced DSBs. First, we found that the axis protein Sycp3 loads adjacent to telomeres and extends inward, suggesting a specific feature common to all telomeres seeds the development of the axis. Second, we found that newly formed axes near telomeres engage in presynaptic co-alignment by a mechanism that depends on DSBs, even when stable juxtaposition of homologous chromosomes at interstitial regions is not yet evident. Third, we were surprised to discover that ~30% of telomeres in early prophase I engage in associations between two or more chromosome ends and these interactions decrease in later stages. Finally, while pairing and synapsis were disrupted in both spo11 males and females, their reproductive phenotypes were starkly different; spo11 mutant males failed to produce sperm while females produced offspring with severe developmental defects. Our results support zebrafish as an important vertebrate model for meiosis with implications for differences in fertility and genetically derived birth defects in males and females. Author Summary Inherent to reproduction is the transmission of genetic information from one generation to the next. In sexually reproducing organisms, each parent contributes an equal amount of genetic information, packaged in chromosomes, to the offspring. Diploid organisms, like humans, have two copies of every chromosome, while their haploid gametes (e.g. eggs and sperm) have only one. This reduction in ploidy depends on the segregation of chromosomes during meiosis, resulting in gametes with one copy of each chromosome. Missegregation of the chromosomes in the parents leads to abnormal chromosome numbers in the offspring, which is usually lethal or has detrimental developmental effects. While it has been known for over a century that homologous chromosomes pair and recombine to facilitate proper segregation, how homologs find their partners has remained elusive. A structure that has been central to the discussion of homolog pairing is the bouquet, or the dynamic clustering of telomeres during early stages of meiosis. Here we use zebrafish to show that the telomere bouquet is the site where key events leading to homologous chromosome pairing are coordinated. Furthermore, we show that deletion of spo11, a gene required for proper recombination in most studied organisms, resulted in very different effects in males and females where males were sterile while females produced deformed progeny.