E-cadherin/HMR-1 and PAR-3 break symmetry at stable cell contacts in a developing epithelium

Abstract

Tissue-wide patterning is essential to multicellular development, requiring cells to individually generate polarity axes and coordinate them in space and time with neighbors. Using the C. elegans intestinal epithelium, we identified a patterning mechanism informed by stabilized cell/cell contact and executed via the scaffolding protein PAR-3 and the transmembrane protein E-cadherin/HMR-1. Intestinal cells break symmetry as PAR-3 and HMR-1 recruit apical determinants into micron-scale local polarity complexes (LPCs) at homotypic contacts. LPCs undergo a HMR-1-based migration to a common tissue midline, thereby establishing tissue-wide polarity. Thus, symmetry breaking results from PAR-3-dependent intracellular polarization coupled to HMR-1-based tissue-level communication that occurs through a non-adhesive signaling role for HMR-1. Intestinal cells gain initial asymmetry from differential contact duration as homotypic contacts last longer than heterotypic contacts, thus providing stable platforms for LPC assembly and offering a logical and likely conserved framework for how internal epithelia with no obvious pre-existing asymmetries can polarize.