Initiation of rotational collective migration in Drosophila through tissue geometry and mechanochemical feedback.

Authors

Sierra Schwabach, Sreejith Santhosh, Audrey Miller Williams, Maureen Cetera, Mattia Serra, Sally Horne-Badovinac

Published in

Proceedings of the National Academy of Sciences of the United States of America. Volume 123. Issue 34. Pages e2528342123. Aug 25, 2026. Epub Aug 18, 2026.

Abstract

Collective migration of epithelial cells drives diverse tissue remodeling processes. In many cases, a free tissue edge works alone or in combination with other external cues to align the cells for collective movement, but how edge-free or closed epithelia become polarized for directed migration without these cues is unclear. Here, we use the rotational migration of the follicular epithelial cells in the Drosophila egg chamber to explore how cells in an edgeless epithelium initiate rotational collective migration, and how the rotational axis is specified. By employing methods for long-term live imaging and delaying the onset of rotation, we show that symmetry breaking can occur at multiple developmental stages and that the atypical cadherin Fat2 promotes local motility at the basal epithelial surface before rotation begins. We then combine experiments with theoretical modeling to identify a positive feedback loop in which planar polarization of Fat2 aligns the front-rear axes of the individual cells in a common direction and the resulting tissue motion leads to the planar polarization of Fat2. This mechanosensitive feedback, coupled with rigid-body dynamics of the egg chamber, can break chiral symmetry and produce sustained rotation in silico. We further propose that mechanical constraints arising from intertissue interactions and tissue geometry ensure that rotation occurs around the anterior-posterior axis. Our findings suggest a biophysical mechanism-combining Fat2-mediated velocity-polarity alignment, rigid-body dynamics, and tissue geometry-by which a closed epithelial tissue can self-organize into persistent, large-scale rotational migration in vivo, expanding current flocking theories.

PMID:
42612006
Bibliographic data and abstract were imported from PubMed on 19 Aug 2026.

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