Institute of Cell Biology, Center for Molecular Biology of Inflammation, University of Münster, 48149 Münster, Germany.
Bioimage Analysis Unit, Institut Pasteur, 75105 Paris, France.
Proc Natl Acad Sci U S A. 2021 Feb 16;118(7). doi: 10.1073/pnas.2018480118.
To study the mechanisms controlling front-rear polarity in migrating cells, we used zebrafish primordial germ cells (PGCs) as an in vivo model. We find that polarity of bleb-driven migrating cells can be initiated at the cell front, as manifested by actin accumulation at the future leading edge and myosin-dependent retrograde actin flow toward the other side of the cell. In such cases, the definition of the cell front, from which bleb-inhibiting proteins such as Ezrin are depleted, precedes the establishment of the cell rear, where those proteins accumulate. Conversely, following cell division, the accumulation of Ezrin at the cleavage plane is the first sign for cell polarity and this aspect of the cell becomes the cell back. Together, the antagonistic interactions between the cell front and back lead to a robust polarization of the cell. Furthermore, we show that chemokine signaling can bias the establishment of the front-rear axis of the cell, thereby guiding the migrating cells toward sites of higher levels of the attractant. We compare these results to a theoretical model according to which a critical value of actin treadmilling flow can initiate a positive feedback loop that leads to the generation of the front-rear axis and to stable cell polarization. Together, our in vivo findings and the mathematical model, provide an explanation for the observed nonoriented migration of primordial germ cells in the absence of the guidance cue, as well as for the directed migration toward the region where the gonad develops.
为了研究控制迁移细胞前后极性的机制，我们使用斑马鱼原始生殖细胞（PGC）作为体内模型。我们发现，泡状突起驱动的迁移细胞的极性可以在细胞前缘开始，表现为未来前缘的肌动蛋白积累和肌球蛋白依赖性的逆行肌动蛋白流向细胞的另一侧。在这种情况下，泡状抑制蛋白（如埃兹蛋白）耗尽的细胞前缘的定义先于那些蛋白积累的细胞后缘的建立。相反，在细胞分裂后，埃兹蛋白在分裂面的积累是细胞极性的第一个标志，这方面的细胞成为细胞背面。总之，细胞前缘和后缘之间的拮抗相互作用导致细胞的强烈极化。此外，我们还表明，趋化因子信号可以偏向细胞前后轴的建立，从而引导迁移细胞向趋化因子浓度更高的部位移动。我们将这些结果与一个理论模型进行了比较，根据该模型，肌动蛋白 treadmilling 流的临界值可以启动一个正反馈回路，从而导致前后轴的产生和稳定的细胞极化。总之，我们的体内发现和数学模型为观察到的原始生殖细胞在没有导向线索的情况下的非定向迁移，以及向性腺发育区域的定向迁移提供了一个解释。
