Modeling the Control of Meiotic Cell Divisions: Entry, Progression, and Exit

Abstract

Upon nitrogen starvation, Schizosaccharomyces pombe exit the mitotic cell cycle and become irreversibly committed to the completion of meiosis program. Meiotic cell divisions are coordinated with sporulation events to produce haploid spores. In the last few decades, experiments on fission yeast have revealed different molecular players involved in two meiotic cell divisions, meiosis I (MI) and meiosis II (MII). How the MI entry, MI-to-MII transition, and MII exit occur because of the dynamics of the regulatory network is not well understood. In this work, we developed a comprehensive mathematical model of the network that describes the temporal dynamics of meiotic progression. The model accounts for the phenotypes of several experimental data (single and multiple mutations). We demonstrate the control strategy involving multiple feedback loops to yield two successive division cycles. The differential regulation of anaphase-promoting complex/cyclosome (APC/C) coactivators and its inhibitors is crucial for the dynamics of both MI-to-MII transition and MII exit. This model generates mechanistic insights that help in further experiments and modeling.

Sporulation: A response to starvation in the fission yeast Schizosaccharomyces pombe

“…In S. pombe , sporulation occurs through gametogenesis during its sexual differentiation response (Shimoda, 2004 ). Although S. pombe normally proliferates as a haploid, exposure to nutrient starvation, such as nitrogen depletion, terminates mitosis; and the cells become diploid through conjugation, leading to an irreversible meiotic program (Dangarh et al, 2020 ; Yamashita et al, 2017 ). Thus, during meiosis I, homologous chromosomes adhere and separate into two nuclei (Yamashita et al, 2017 ).…”

Periodicity in the embryo: emergence of order in space, diffusion of order in time

“…While it is not discussed in this paper, gene expression fluctuations and stochastic noise in gene expression drives heterogeneity in division timing and even timing of differentiation [29,30]. In particular, a focus on the molecular biology of the cell cycle across groups of developmental cells [31,32] can provide more information about how fluctuations work in general at the single-cell level. Yet single cells acting in synchrony (or in the aggregate) define the patterns observed in our empirical data.…”

Periodicity in the embryo: Emergence of order in space, diffusion of order in time

“…While it is not discussed in this paper, gene expression fluctuations and stochastic noise in gene expression drives heterogeneity in division timing and even timing of differentiation [37,38]. In particular, a focus on the molecular biology of the cell cycle across groups of developmental cells [39,40] can provide more information about how fluctuations work in general at the single-cell level. Yet single cells acting in synchrony (or in the aggregate) define the patterns observed in our empirical data.…”