A Newly Identified Cilium in Meiosis - Deciphering the Principles and Mechanisms of the Zygotene Cilium | ZygoCiliaAct | Projekt | Informationsblatt | HORIZON | CORDIS

Projektbeschreibung

Neuartige zelluläre Komponenten bei der Zellteilung

Bei der Meiose handelt es sich um den Prozess der Zellteilung während der Fortpflanzung, bei dem sich die Chromosomen nebeneinander anordnen. Dieser Prozess ermöglicht den Austausch von genetischem Material und trägt zur genetischen Vielfalt der Nachkommen bei. Das vom Europäischen Forschungsrat finanzierte Projekt ZygoCiliaAct zielt darauf ab, die Mechanismen zu beschreiben, die die Chromosomenpaarung regulieren. Das Projekt stützt sich auf die jüngste Entdeckung eines bisher unbekannten Ziliums – das Zygoten-Zilium –, das aus der Eizelle und der Spermatozyte herausragt und mit den meiotischen Chromosomen interagiert. Die Forschenden verfolgen das Ziel, die funktionellen mechanischen und regulatorischen Komponenten des Zygoten-Ziliums aufzudecken und die Signale zu entschlüsseln, die die Meiose steuern, um so unser Wissen über Entwicklungsbiologie und Fortpflanzung zu erweitern.

Ziel

A hallmark of meiosis is chromosomal pairing, which for decades has been a major focus in the field. However, the nuclear events of meiosis occur in the cellular context of a differentiating gamete, and pairing depends on cytoplasmic counterparts, by mechanisms that are conserved from yeast to mammals. These are essential for fertility, but how cytoplasmic counterparts of chromosomal pairing are regulated has remained enigmatic. We uncovered a previously unrecognized cilium in meiosis – the zygotene cilium, in both males and females and in zebrafish and the mouse, which completes the mechanical cytoplasmic pairing machinery, and extracellularly extend between oocytes within a conserved cellular hub, called the germline cyst. We established the ground-breaking observations that the cilium is essential for chromosomal pairing, prophase progression and cyst morphogenesis, ovary development and fertility. These uncover the novel concept of a cilium as a critical player in meiosis, propose a cellular paradigm that cilia can control chromosomal dynamics, and shed new light on reproduction phenotypes in human ciliopathies.
The zygotene cilium now allows us to zoom-out from the nuclear events of prophase to the complete cellular and developmental program of meiosis. Utilizing our holistic morphological approach in-vivo, ZygoCiliaAct will ambitiously achieve this goal in three related but independent aims. We will uncover zygotene cilium functional mechanical and regulatory components (Aim 1), decipher the ciliary developmental signals that govern meiotic prophase progression and cyst morphogenesis (Aim 2), and expand our findings to investigation in testes, as well as use zebrafish as a new model to decipher mechanisms of human ciliopathic proteins (Aim 3). With ZygoCiliaAct we are finally poised to break new grounds in unraveling long-sought-after fundamental questions cell, developmental, cilia, and reproductive biology, and advance reproduction and ciliopathy medicine.