Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139.
Department of Physics, Massachusetts Institute of Technology, Cambridge, MA 02139.
Proc Natl Acad Sci U S A. 2021 Mar 9;118(10). doi: 10.1073/pnas.2019749118.
From insects to mice, oocytes develop within cysts alongside nurse-like sister germ cells. Prior to fertilization, the nurse cells' cytoplasmic contents are transported into the oocyte, which grows as its sister cells regress and die. Although critical for fertility, the biological and physical mechanisms underlying this transport process are poorly understood. Here, we combined live imaging of germline cysts, genetic perturbations, and mathematical modeling to investigate the dynamics and mechanisms that enable directional and complete cytoplasmic transport in egg chambers. We discovered that during "nurse cell (NC) dumping" most cytoplasm is transported into the oocyte independently of changes in myosin-II contractility, with dynamics instead explained by an effective Young-Laplace law, suggesting hydraulic transport induced by baseline cell-surface tension. A minimal flow-network model inspired by the famous two-balloon experiment and motivated by genetic analysis of a myosin mutant correctly predicts the directionality, intercellular pattern, and time scale of transport. Long thought to trigger transport through "squeezing," changes in actomyosin contractility are required only once NC volume has become comparable to nuclear volume, in the form of surface contractile waves that drive NC dumping to completion. Our work thus demonstrates how biological and physical mechanisms cooperate to enable a critical developmental process that, until now, was thought to be mainly biochemically regulated.
从昆虫到老鼠,卵母细胞在与滋养细胞姐妹类似的囊泡中发育。在受精之前,滋养细胞的细胞质内容物被转运到卵母细胞中,随着其姐妹细胞的退化和死亡,卵母细胞生长。尽管这对于生育能力至关重要,但这种转运过程的生物学和物理机制还知之甚少。在这里,我们结合生殖细胞囊泡的实时成像、遗传干扰和数学建模,研究了使卵室中定向和完全细胞质转运的动力学和机制。我们发现,在“滋养细胞(NC)倾倒”过程中,大部分细胞质是独立于肌球蛋白-II 收缩性变化而转运到卵母细胞中的,其动力学可以用有效杨氏拉普拉斯定律来解释,这表明基底细胞表面张力诱导的液压转运。受著名的两个气球实验启发并受肌球蛋白突变体遗传分析驱动的简化流动网络模型正确预测了转运的方向性、细胞间模式和时间尺度。长期以来,人们认为通过“挤压”触发转运,但只有当 NC 体积变得与核体积相当时,肌动球蛋白收缩性的变化才是必需的,其形式是以表面收缩波推动 NC 倾倒完成。因此,我们的工作展示了生物和物理机制如何合作,以实现这一关键的发育过程,而直到现在,人们还认为这个过程主要是通过生化调节来实现的。