Speaker: Yaniv Elkouby, The Hebrew University of Jerusalem
Topic: Ciliary control of chromosomal pairing mechanics in meiosis, and cellular control of phase-separation in oocyte polarity – two tales, common cellular machinery
The Elkouby lab employs a holistic morphological approach to understand the cell and developmental biology of early oogenesis in-vivo in zebrafish ovaries. In my talk, I will focus on two recent stories from my lab. These entail distinct processes in oocyte development, coordinated by a common and unique cellular organization.
A hallmark of meiosis is chromosomal pairing, which requires telomere tethering and rotation on the nuclear envelope through microtubules, driving chromosome homology searches. Telomere pulling toward the centrosome forms the “zygotene chromosomal bouquet.” We identified the “zygotene cilium” in oocytes. This cilium provides a cable system for the bouquet machinery and extends 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.
We previously showed that the bouquet apparatus breaks the oocyte symmetry. Oocyte polarity along the animal-vegetal axis is essential for oogenesis and embryogenesis and is established by a large RNA-protein granule, called the Balbiani body (Bb), a conserved oocyte feature from insects to humans. In Bb formation, Bb granules first polarized to the bouquet centrosome, at bouquet stages, and by the bouquet microtubule apparatus. Bb granules then nucleate within a nuclear cleft, giving rise to the mature structure, but the mechanisms have been unknown. We provide live microscopy, molecular, and biochemical evidence to show that Bb granules initially undergo liquid-liquid phase separation, and then gradually lipid-solid phase- separation in forming the mature Bb. Further, dynein-mediated trafficking is required for Bb granule localized aggregation, and a meshwork of microtubules then scaffolds aggregated granules, maintaining Bb formation. Phase-separation is often viewed as a self-assembly process. We uncovered mechanisms of cellular control over this phenomenon in vivo.