Dynamic organelle distribution initiates actin-based spindle migration in mouse oocytes

Xing Duan,Haiyang Wang,Edwin Angelo Morales,Yizeng Li,Jing Yang,Devin B Mair,Denis Wirtz,Sean X Sun,Pei-Hsun Wu,Petr Kalab,Kexi Yi,Rong Li,Fengli Guo

doi:10.1038/s41467-019-14068-3

Abstract

Migration of meiosis-I (MI) spindle from the cell center to a sub-cortical location is a critical step for mouse oocytes to undergo asymmetric meiotic cell division. In this study, we investigate the mechanism by which formin-2 (FMN2) orchestrates the initial movement of MI spindle. By defining protein domains responsible for targeting FMN2, we show that spindle-periphery localized FMN2 is required for spindle migration. The spindle-peripheral FMN2 nucleates short actin bundles from vesicles derived likely from the endoplasmic reticulum (ER) and concentrated in a layer outside the spindle. This layer is in turn surrounded by mitochondria. A model based on polymerizing actin filaments pushing against mitochondria, thus generating a counter force on the spindle, demonstrated an inherent ability of this system to break symmetry and evolve directional spindle motion. The model is further supported through experiments involving spatially biasing actin nucleation via optogenetics and disruption of mitochondrial distribution and dynamics.

Highlights

Migration of meiosis-I (MI) spindle from the cell center to a sub-cortical location is a critical step for mouse oocytes to undergo asymmetric meiotic cell division
Expression of each fragment through mRNA injection in MI oocytes revealed that the aa 1–135 region of FMN2 is sufficient for FMN2 cortical localization, whereas aa 275–734 is sufficient for localization to the spindle periphery (Fig. 1b)
The results described above provide mechanistic insights into how FMN2-nucleated actin filaments drive the first phase of spindle movement and the initiation of symmetry breaking

Summary

Introduction

Migration of meiosis-I (MI) spindle from the cell center to a sub-cortical location is a critical step for mouse oocytes to undergo asymmetric meiotic cell division. The spindle-peripheral FMN2 nucleates short actin bundles from vesicles derived likely from the endoplasmic reticulum (ER) and concentrated in a layer outside the spindle This layer is in turn surrounded by mitochondria. A model based on polymerizing actin filaments pushing against mitochondria, generating a counter force on the spindle, demonstrated an inherent ability of this system to break symmetry and evolve directional spindle motion. 1234567890():,; The maturation of mammalian oocytes involves two consecutive asymmetric divisions that produce a large egg and two small polar bodies (PB) These asymmetric cell divisions depend on the eccentric positioning of the meiotic spindle adjacent to a polarized actomyosin-rich cortical domain[1,2,3]. We performed experiments to validate several predictions of the model

Methods

Results

Conclusion