Control of meiotic chromosomal bouquet and germ cell morphogenesis by the zygotene cilium

Abstract

A hallmark of meiosis is chromosomal pairing, which requires telomere tethering and rotation on the nuclear envelope via microtubules, driving chromosome homology searches. Telomere pulling toward the centrosome forms the “zygotene chromosomal bouquet”. Here, we identified the “zygotene cilium” in oocytes. This cilium provides a cable system for the bouquet machinery, extending throughout the germline cyst. Using zebrafish mutants and live manipulations, we demonstrate that the cilium anchors the centrosome to counterbalance telomere pulling. The cilium is essential for bouquet and synaptonemal complex formation, oogenesis, ovarian development, and fertility. Thus, a cilium represents a conserved player in zebrafish and mouse meiosis, which sheds light on reproductive aspects in ciliopathies, and suggests that cilia can control chromosomal dynamics.

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

“…The bouquet polarization is a transient conformation of the chromosomal ends that favors the pairing process between homologous chromosomes [71]. Recent reports in zebrafish oogenesis demonstrated a correlation between the zygotene cilia and the bouquet conformation, suggesting that absence of cilia or their incorrect formation affect synapsis progression [36]. However, we could not find any correlation between the presence of cilia and the chromosomal bouquet conformation in mice.…”

“…Quantitative analysis showed that around 20% of the spermatocytes at zygotene showed this hair-like structure (n=100 spermatocytes at zygotene per individual, three biological replicates). This hair-like staining pattern of AcTub in spermatocytes at early zygotene is consistent with the solitary projection that is formed when primary cilia assemble in both somatic [12] and meiotic cells [36]. These zygotene cilia were present when only two centrioles are detected, which indicates that mouse meiotic cilia are assembled 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].…”

“…Meiotic cilium in zebrafish oocytes favors the polarization of the chromosome telomeres, which are anchored to the nuclear envelope (NE), forming the so-called bouquet configuration [36]. To test whether the mouse zygotene cilium in spermatocytes is related to the bouquet conformation, we performed a double immunodetection of the telomeric double-stranded TTAGGG repeat binding proteins (TRF2) and AcTub.…”

Insights Gained From Zebrafish Models for the Ciliopathy Joubert Syndrome

“…Indeed, often only a specific phenotype of interest was investigated and described. Phenotypic characterization was mostly conducted on zygotic mutant zebrafish since adult zebrafish harboring mutations in JBTS-genes often exhibit reduced viability, scoliosis and reduced fertility ( Mytlis et al, 2022 ), making the generation of maternal zygotic mutants via natural matings challenging (requires in vitro fertilization and/or generation of germline mosaic fish) ( Ben et al, 2011 ).…”