Institute of Molecular Life Sciences, University of Zürich, Zürich, Switzerland.
Molecular Life Science PhD Program, University of Zürich and ETH Zürich, Zürich, Switzerland.
PLoS Biol. 2024 Aug 23;22(8):e3002775. doi: 10.1371/journal.pbio.3002775. eCollection 2024 Aug.
Germ cell apoptosis in Caenorhabditis elegans hermaphrodites is a physiological process eliminating around 60% of all cells in meiotic prophase to maintain tissue homeostasis. In contrast to programmed cell death in the C. elegans soma, the selection of germ cells undergoing apoptosis is stochastic. By live-tracking individual germ cells at the pachytene stage, we found that germ cells smaller than their neighbors are selectively eliminated through apoptosis before differentiating into oocytes. Thus, cell size is a strong predictor of physiological germ cell death. The RAS/MAPK and ECT/RHO/ROCK pathways together regulate germ cell size by controlling actomyosin constriction at the apical rachis bridges, which are cellular openings connecting the syncytial germ cells to a shared cytoplasmic core. Enhancing apical constriction reduces germ cell size and increases the rate of cell death while inhibiting the actomyosin network in the germ cells prevents their death. We propose that actomyosin contractility at the rachis bridges of the syncytial germ cells amplifies intrinsic disparities in cell size. Through this mechanism, the animals can adjust the balance between physiological germ cell death and oocyte differentiation.
秀丽隐杆线虫雌雄同体生殖细胞凋亡是一个生理过程,可清除减数分裂前期约 60%的所有细胞,以维持组织内稳态。与线虫体细胞的程序性细胞死亡不同,发生凋亡的生殖细胞的选择是随机的。通过在粗线期对单个生殖细胞进行实时追踪,我们发现,在分化为卵母细胞之前,比其相邻细胞小的生殖细胞通过凋亡被选择性清除。因此,细胞大小是生理生殖细胞死亡的一个强有力的预测指标。RAS/MAPK 和 ECT/RHO/ROCK 途径通过控制连接合胞体生殖细胞和共享细胞质核心的顶端脊索桥的肌动球蛋白收缩来共同调节生殖细胞大小,脊索桥是连接合胞体生殖细胞的细胞开口。增强顶端收缩会减小生殖细胞的大小并增加细胞死亡的速度,而抑制生殖细胞中的肌动球蛋白网络则可以防止它们死亡。我们提出,合胞体生殖细胞脊索桥上的肌动球蛋白收缩放大了细胞大小的内在差异。通过这种机制,动物可以在生理生殖细胞死亡和卵母细胞分化之间调整平衡。