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bioRxiv · 10.64898/2026.02.23.707595

Synthetic reconstitution of planar polarity initiation reveals collective migration as a symmetry-breaking cue

Wallach, L. A.·Thomas, C. D.·Li, P.
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Abstract

Planar cell polarity (PCP) organizes cellular behaviors along tissue axes, yet how symmetry is broken to initiate polarity across initially symmetric tissues remains unknown. We reconstituted tissue-scale polarity emergence ex vivo using an engineered epithelial system. A collective migration cue induces front-back enrichment of CELSR junctions, establishing aligned multicellular polarity that tracks migration direction and speed. A migration-onset wave consistently precedes the polarity-initiation wave, indicating that individual cells directly interpret the global cue rather than acquire polarity through intercellular relay. Strikingly, CELSR polarity arises without reciprocal VANGL-FZD interactions, identifying CELSR as the driver for planar polarization. These findings reveal how a global migratory cue can break symmetry and coordinate PCP across molecular, cellular, and tissue scales, providing a framework for engineering polarized tissues.

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Wallach, L. A., Thomas, C. D., Li, P.. 2026-02-25. Synthetic reconstitution of planar polarity initiation reveals collective migration as a symmetry-breaking cue. https://doi.org/10.64898/2026.02.23.707595

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