A Newly Identified Cilium in Meiosis - Deciphering the Principles and Mechanisms of the Zygotene Cilium

Introduction

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.

Discovery of the Zygotene Cilium

We uncovered a previously unrecognized cilium in meiosis – the zygotene cilium, in both males and females and in zebrafish and the mouse. This cilium completes the mechanical cytoplasmic pairing machinery and extracellularly extends between oocytes within a conserved cellular hub, called the germline cyst.

Ground-breaking Observations

We established the ground-breaking observations that the cilium is essential for:

1. Chromosomal pairing
2. Prophase progression
3. Cyst morphogenesis
4. Ovary development
5. Fertility

These findings 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 reproductive phenotypes in human ciliopathies.

Research Goals

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:

1. Uncover zygotene cilium functional mechanical and regulatory components (Aim 1)
2. Decipher the ciliary developmental signals that govern meiotic prophase progression and cyst morphogenesis (Aim 2)
3. 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)

Conclusion

With ZygoCiliaAct, we are finally poised to break new ground in unraveling long-sought-after fundamental questions in cell, developmental, cilia, and reproductive biology, and advance reproduction and ciliopathy medicine.