The Wnt co-receptor Arrow-LRP5/6 is required for Planar Cell Polarity establishment in Drosophila

Abstract Wnt-signaling, via β-catenin or the planar cell polarity (PCP) branch, is crucial for development, tissue homeostasis, and linked to many diseases. LRP5/6, arrow ( arr ) in Drosophila , is the obligate co-receptor in Wnt/β-catenin signaling, with ligand binding to a Frizzled (Fz) family member and LRP5/6 mediating formation of the signalosome complex with Dishevelled (Dsh/Dvl in mammals) and Axin. Current models for Wnt/PCP signaling omit Arr/LRP5/6 and the notion is that it functions without these co-receptors. Here we show that arr/LRP5/6 is positively required in Wnt/PCP signaling. In Drosophila , loss of arr results in PCP mediated cellular orientation defects, aberrant wing hair formation, and loss of polarity, as described for core PCP factors fz, fmi/Celsr, and dsh . In the eye, arr mutant tissue displays cell fate changes in photoreceptors R3/R4 and chirality defects, classical PCP phenotypes. During Wnt/PCP establishment, defects are manifest as reduced levels of Fmi/Celsr and Dsh along with loss of their asymmetric localization. Functional interactions indicate that Fz can recruit Arr, and this potentiates Fz and Dsh function in PCP signaling in all tissues tested. Taken together, our data support an essential Arr/LRP5/6 function in promoting Wnt/Fz-Dsh PCP-complex activity.