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

Abstract

SummaryTissue-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.

The biosynthetic-secretory pathway, supplemented by recycling routes, determines epithelial membrane polarity

“…Basement membrane-associated extracellular matrix signals, although so far elusive in the C. elegans intestine (46,49), could, in principle, organize the actin cytoskeleton (as, for instance, in the Drosophila follicular epithelium) (75)(76)(77) or directly polarize trafficking routes from the basolateral membrane, as demonstrated in MDCK cysts (78). Finally, lateral membrane-based PAR-3 and HMR-1/cadherin complexes were recently proposed as intercellular polarity triggers in the C. elegans intestine; however, they must, like PARs and junctions, themselves be polarized (79).…”

Branched-chain actin dynamics polarizes vesicle trajectories and partitions apicobasal epithelial membrane domains

“…No ECM-derived polarity signals have yet been identified in the C. elegans intestine ( 26 , 81 ), but multiple basement membrane components have now been shown to be expressed in the early-embryonic intestine ( 82 ). Lateral cortical polarity complexes, consisting of PAR-3 and the junction component HMR-1/cadherin, were recently suggested as intra-intestinal, albeit extracellular, polarity triggers in the C. elegans intestine ( 83 ). They must, however, like PARs and junctions, themselves be polarized to apical and apico-lateral domains, respectively (discussed above).…”