Wnt signaling and tissue tension reconstitute planar cell polarity in vitro

Abstract

Planar cell polarity (PCP) aligns cells within the plane of a tissue through asymmetric localization of core PCP proteins. In vivo, PCP arises from integration of biochemical signaling and mechanical inputs, making it challendging to reconstruct in vitro. Here we reconstitute PCP in cultured MDCK epithelial cells using Wnt signaling, collective migration, and Prickle3 overexpression. Loss of Vangl1 disrupts reconstituted PCP, directional collective migration, and propagation of ERK traveling waves. Orthogonal manipulation of signaling and mechanics show that tissue tension contributes to establishing a polarity axis, but not its direction, whereas local Wnt input specifies polarity direction. Together, these inputs generate tissue-wide vectorial polarity. This system provides a tractable framework for dissecting how signaling and mechanics are integrated to organize tissues. TeaserWnt signaling and tissue tension reconstitute planar cell polarity in cultured epithelial cells through core-component interdependence and ERK dynamics.