Schwabach Sierra, Santhosh Sreejith, Williams Audrey Miller, Cetera Maureen, Serra Mattia, Horne-Badovinac Sally
Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, IL, USA.
Department of Physics, University of California, San Diego, CA, USA.
bioRxiv. 2025 Sep 4:2025.09.03.674060. doi: 10.1101/2025.09.03.674060.
Collective migration of epithelial cells drives diverse tissue remodeling processes. In many cases, a free tissue edge polarizes the cells to promote directed motion, but how edge-free or closed epithelia initiate migration remains unclear. Here, we show that the rotational migration of follicular epithelial cells in the egg chamber is a self-organizing process. Combining experiments and theoretical modeling, we identify a positive feedback loop in which the mechanosensitive behavior of the atypical cadherin Fat2 synergizes with the rigid-body dynamics of the egg chamber to both initiate and sustain rotation. Mechanical constraints arising from cell-cell interactions and tissue geometry further align this motion around the egg chamber's anterior-posterior axis. Our findings reveal a biophysical mechanism - combining Fat2-mediated velocity-polarity alignment, rigid-body dynamics, and tissue geometry - by which a closed epithelial tissue self-organizes into persistent, large-scale rotational migration , expanding current flocking theories.
上皮细胞的集体迁移驱动了多种组织重塑过程。在许多情况下,游离的组织边缘会使细胞极化以促进定向运动,但无边缘或封闭的上皮细胞如何启动迁移仍不清楚。在这里,我们表明卵室中卵泡上皮细胞的旋转迁移是一个自组织过程。结合实验和理论模型,我们确定了一个正反馈回路,其中非典型钙黏蛋白Fat2的机械敏感行为与卵室的刚体动力学协同作用,以启动和维持旋转。细胞间相互作用和组织几何结构产生的机械约束进一步使这种运动围绕卵室的前后轴排列。我们的研究结果揭示了一种生物物理机制——结合Fat2介导的速度-极性排列、刚体动力学和组织几何结构——通过这种机制,封闭的上皮组织自组织成持续的大规模旋转迁移,扩展了当前的集群理论。