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

Abstract

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.

Centric Fusions behind the Karyotype Evolution of Neotropical Nannostomus Pencilfishes (Characiforme, Lebiasinidae): First Insights from a Molecular Cytogenetic Perspective

“…From the cytogenetic standpoint only, certain repetitive DNA markers, including 5S and 18S rDNA, have been formerly found to be involved in the formation of centric fusions (e.g., [39][40][41]). In the case of rDNAs, this may be possibly linked with the susceptibility of these tandemly repeated clusters to double-stranded DNA breaks, perhaps resulting from (1) a frequent rRNA transcription and thus break-prone R-loop emergence, (2) intermingling of NOR (Nuclear Organizer Region)-bearing chromosomes in the interphase nucleus, or (3) possible association of rDNA-bearing sites during the meiotic prophase I [42][43][44][45][46][47][48]. With a few exceptions, the terminal position of the 18S rDNA loci on chromosomes appears to be a common feature for all Lebiasinidae genera analyzed up to now (i.e., Nannostomus, Pyrrhulina, Lebiasina, and Copeina) ( [19][20][21][22], this study).…”

Mixing and Matching Chromosomes during Female Meiosis

“…Most chromosomes are subtelomeric and submetacentric, and only two are metacentric [99]. It is only recently that the timing of meiotic progression has been described systematically in males and females [17]. It was found that the formation of a telomere bouquet was a key event of early meiosis in zebrafish.…”

“…Indeed, DSB formation, homologues pairing and synapsis, all start at, or close to, telomeric ends, when telomeres cluster in leptotene/early zygotene. Thus, there is a dramatic polarisation of DSBs and synapsis at telomeres [17,100]. Synapsis then proceeds from telomeres inward to the rest of the chromosome.…”

“…Studies on fixed samples set the stage for further analysis of chromosome movements and dynamics [17,100]. Microtubule inhibitors are known to disrupt both the formation of the bouquet and of the Balbiani body (a structure containing mitochondria, ER and Golgi vesicles) [47].…”

Rad21l1 cohesin subunit is dispensable for spermatogenesis but not oogenesis in zebrafish

“…Although homologs of RAD21L have been identified in other vertebrate genomes, there is a dearth of studies of this cohesin in vertebrates other than mouse. Zebrafish has emerged as an excellent model to use genetic approaches to study the chromosome events in meiosis [38][39][40][41]. Both sexes produce gametes throughout their lives, thus providing a window to study sexually dimorphic features of female and male meiosis.…”