We uncovered a previously unrecognized cilium in early oocytes, which completes the cytoskeletal machinery of meiotic chromosomal pairing, and is conserved in male and females in both zebrafish and mice (Mytlis, Kumar et al., 2022, Science, highlighted by Dev. Cell and preLihgts).
A hallmark of meiosis is chromosomal pairing, which in contrast to a typical textbook view, is regulated from the cytoplasm. Chromosomal pairing requires telomere tethering and rotation on the nuclear envelope via dynein and microtubules, which shuffle chromosomes in the nucleus, driving their homology searches.
Telomeres are ultimately pulled towards the centrosome, looping their chromosomes to the other side, forming the “zygotene chromosomal bouquet” configuration, which is conserved from yeast to mammals. However, despite its discovery in 1885, how the cytoplasmic counterparts of bouquet formation are mechanically regulated was unknown.
We discovered the “zygotene cilium” in zebrafish – a previously unrecognized cilium in oocytes that completes the bouquet cytoplasmic machinery of chromosomal pairing and extends through the germline cyst, a conserved cellular hub of developing oocytes. Using ciliary mutants and live manipulations, we demonstrated that the cilium anchors the centrosome to counterbalance telomere pulling. The cilium is essential for bouquet and synaptonemal complex formation, cyst morphogenesis, ovarian development, and fertility.
After decades of research in the field, the cilium provides a major leap forward in generating a more complete and integrative understanding of meiosis, germ cells, gonad development, and cilia biology (Mytlis et al., 2023, Curr. Opin. In Cell Biol.). Strikingly, the cilium is conserved in human fetal ovaries (in-preparation), offering a new platform to identify overlooked mechanisms in reproduction deficiencies.
The discovery of the zygotene cilium is just the tip of the iceberg. In our ERC CoG funded program we are currently working to decipher principles and mechanisms of the zygotene cilium. We aim to uncover the mechanical and regulatory components of the cilium in anchoring the centrosome, decipher its signaling activity in controlling oocyte morphogenesis, and establish models to identify mechanisms of infertility.
