Synthetic reconstitution of planar polarity initiation reveals principles of symmetry breaking across scales

Development often relies on molecular prepatterning over large tissue scales, and how these patterns emerge is an essential question. Planar cell polarity (PCP), manifested as asymmetric distribution of junctional proteins within individual cells and coordinated across entire tissues, is a key module controlling tissue morphogenesis and organization. How tissues break symmetry to initiate PCP remains unknown. By reconstituting polarity initiation ex vivo using engineered epithelial cells, we found that collective migration acts as the symmetry-breaking cue, inducing front-back enrichment of CELSR junctions and establishing aligned multicellular CELSR polarity. Individual cells directly interpret the migration cue and remain sensitive to it. Strikingly, CELSR polarity arises without reciprocal VANGL-FZD interactions, identifying CELSR as the driver for polarity initiation. These findings reveal that collective migration initiates and coordinates PCP across molecular, cellular, and tissue scales, demonstrating that morphogenetic events act as a trigger for spatial pattern emergence.