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

ABSTRACT: Tissue morphogenesis requires the spatial control over actomyosin contractility to drive cell shape changes. How developmental patterning information controls cell mechanics is poorly understood. In the Drosophila embryo ectoderm, Myosin-II is enriched at the interface between antero-posterior neighboring cells, leading to planar polarized cell intercalation. G protein-coupled receptors (GPCRs) are required for planar polarized Myosin-II activation at junctions and Toll receptors provide a positional code underlying this process. How Toll receptors polarize actomyosin contractility remains unknown. Here we report that cells expressing different levels of a single Toll receptor Toll-8 activate Myosin-II at their interface. Surprisingly, the Toll-8 intracellular domain is not required for signaling at cell interfaces suggesting signaling by proxy. We found that Toll-8 forms a molecular complex with the adhesion GPCR Cirl/Latrophilin that is required for Toll-8 dependent junctional Myosin-II activation. Strikingly, the interfaces between Cirl expressing and cirl mutant cells also activate Myosin-II suggesting that Toll-8 induces Cirl asymmetric signaling at cell interfaces. We further showed that Toll-8 recruits Cirl both in trans and in cis, inducing asymmetric Cirl localization at the boundary of the Toll-8 expression domain. Finally, we found that Toll-8 and Cirl exhibit dynamic interdependent planar polarization when neighboring cells express different levels of Toll-8. Through this feedback, Toll-8 and Cirl self-organize planar polarized signaling.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Drosophila Melanogaster (fruit Fly)

TISSUE(S): Embryo

SUBMITTER: AUDEBERT Stephane  

LAB HEAD: Audebert Stephane

PROVIDER: PXD017895 | Pride | 2021-04-22

REPOSITORIES: Pride