Planar cell polarity aligns epithelial migration to coordinate tissue architecture and functional zonation

Abstract

Epithelial tissues must coordinate collective migration with functional specialization to maintain organ integrity, but the mechanisms linking these processes remain unknown. Here, we define the planar cell polarity (PCP) pathway as a master coordinator that translates molecular asymmetry into tissue-scale organization during postnatal intestinal development. We show that PCP drives the developmental transition from random to linear epithelial migration by aligning actin-based basal protrusions and polarizing basement membrane integrins. This creates coherent cellular streams that form characteristic villus ribbons. Strikingly, we discover that disrupting this migration coherence directly perturbs functional zonation, as loss of PCP causes disordered migration that expands specialized metabolic domains beyond their spatial boundaries. These findings reveal a previously unrecognized principle of epithelial organization: directional collective migration actively maintains functional compartmentalization, establishing migration pattern as a fundamental determinant of how tissues preserve specialized function during continuous turnover.