Formation of polarized contractile interfaces by self-organized Toll-8/Cirl GPCR asymmetry

Abstract

During development, interfaces between cells with distinct genetic identities elicit signals to organize local cell behaviors driving tissue morphogenesis. The Drosophila embryonic axis extension requires planar polarized enrichment of Myosin-II powering oriented cell intercalations. Myosin-II levels are quantitatively controlled by G protein-coupled receptor (GPCR) signaling whereas Myosin-II polarity requires patterned expression of several Toll receptors. How Toll receptors polarizes Myosin-II, and how this involves GPCRs, remain unknown. Here we report that differential expression of a single Toll receptor, Toll-8, polarizes Myosin-II via a novel binding partner, the adhesion GPCR Cirl/Latrophilin. Asymmetric expression of Cirl is sufficient to enrich Myosin-II and Cirl localization is asymmetric at Toll-8 expression boundaries. Exploring the process dynamically, we reveal that Toll-8 and Cirl exhibit mutually dependent planar polarity in response to quantitative differences in Toll-8 expression between neighboring cells. Collectively, we propose that a novel cell surface protein complex Toll-8/Cirl self-organizes to generate local asymmetric interfaces essential for planar polarization of contractile interfaces.