Cilia regulate meiotic recombination in zebrafish

Abstract

Meiosis is essential for evolution and genetic diversity in almost all sexual eukaryotic organisms. The mechanisms of meiotic recombination, such as synapsis, have been extensively investigated. However, it is still unclear whether signals from the cytoplasm or even outside of the cell can regulate the meiosis process. Cilia are microtubule-based structures that protrude from cell surface and function as signaling hubs to sense extracellular signals. Here, we reported an unexpected and critical role of cilia during meiotic recombination. During gametogenesis of zebrafish, cilia were specifically present in the prophase stages of both spermatocytes and primary oocytes. By developing a novel germ cell-specific CRISPR/Cas9 system, we demonstrated that germ cell-specific depletion of ciliary genes resulted in compromised double strand break repair, reduced crossover formation, and increased germ cell apoptosis. Our study reveals a previously undiscovered role for cilia during meiosis and suggests that extracellular signals may regulate meiotic recombination via this particular organelle.

The male mouse meiotic cilium emanates from the mother centriole at zygotene prior to centrosome duplication

“…Our results demonstrate that zygotene cilia in mouse spermatocytes contain acetylated Tubulin -AcTub-, similarly to the zygotene cilia in zebrafish spermatocytes and oocytes [36,37].…”

“…This provides a scenario that challenges the assumption that primary cilia are antagonistic with cell division, as it has to be taken into account that cells at zygotene have already started meiotic cell division [49]. Apart from our work and the recent advances in zebrafish gametogenesis [36, 37], another previous report also pointed at the presence of primary cilia during D. melanogaster spermatogenesis. Moreover, they suggested that these cilia were stable through both meiotic divisions in dividing spermatocytes with yet unknown functions [50].…”

“…This conformation is extremely short-lived in this species and most likely precedes the formation of the cilia. On the other hand, the zebrafish cilium has also been related to recombination regulation [37]. We cannot make any considerations in this regard, as the relationship between cilia and recombination in mice should require additional approaches.…”

“…The first one described the zygotene cilium in zebrafish oocytes, pointing to an evolutionary conservation of this structure in mammals, but suggesting that ciliary structures in mouse spermatocytes were very short, barely extending beyond the basal body [36]. The second study proposed that germ cell-specific depletion of ciliary genes resulted in compromised double-strand break repair, reduced crossover formation, and increased germ cell apoptosis in zebrafish spermatogenesis [37]. We here show a detailed description of the mouse meiotic cilium, and we hypothesize that they are primary cilia.…”

“…However, these effects were attributed to the malfunction of the primary cilium in somatic cells of the testicle, like Sertoli and peritubular myoid cells, or cells of the epididymis [35]. More recently, the presence of cilia in meiotic cells has been reported in zebrafish oogenesis [36] and spermatogenesis [37]. These reports indicate that the meiotic cilium may be an important regulator of chromosome polarization and recombination.…”