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Tissue geometry and mechanochemical feedback initiate rotational migration in Drosophila

Schwabach, S.; Santhosh, S.; Williams, A. M.; Cetera, M.; Serra, M.; Horne-Badovinac, S.

2025-09-04 cell biology
10.1101/2025.09.03.674060 bioRxiv
Show abstract

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 Drosophila 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 chambers 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 in vivo, expanding current flocking theories.

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