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. Current models for Wnt/PCP signaling omit Arr-LRP5/6 and PCP is presumed functioning without these co-receptors. Here we show that arr-LRP5/6 is fully required in Wnt/PCP signaling. In Drosophila, loss of arr results in aberrant PCP mediated cellular orientation and loss of polarity coordination in wings, comparable to core PCP factors mutations, with defects manifest as loss of asymmetric PCP factor localization and reduced levels of Dishevelled (Dsh) with centrally forming wing hairs. In the eye, arr mutant tissue displays phenotypes with defects in chirality and photoreceptors R3 and R4 cell fates. Functional interactions indicate that Fz can recruit Arr, and Arr potentiates Fz-Dsh PCP signaling in all tissues tested. Furthermore, arr-LRP5/6 sensitizes the ligand pair Wg, Wnt4 with the receptor fz, and the core PCP factors fmi and Vang/stbm to cause PCP defects in heterozygous conditions. Our data support a core PCP function of Arr-LRP5/6, promoting Wnt/Fz-Dsh PCP-complex activity.
Related
- Dishevelled-mediated clustering stabilizes Frizzled6 and Vangl2 to establish planar cell polarity in the mammalian skin
- Proapoptotic RHG proteins and mitochondria are required for sensory dendrite pruning in Drosophila
- Loss of residues required for β-arrestin recruitment in the calcium-sensing receptor C-terminal tail may contribute to hypocalcemia
- Phosphorylated HPV‑16 E7 disrupts planar cell polarity in cervical cancer cells through vangl1 dysregulation
- EGFR-Aurka Signaling Rescues Polarity and Regeneration Defects in Dystrophin-Deficient Muscle Stem Cells by Increasing Asymmetric Divisions
BibTeX
@article{weber2026coreceptor,
title = {{The Wnt co-receptor Arrow-LRP5/6 is required for planar cell polarity establishment in Drosophila}},
author = {Ursula Weber and Reza Farhadifar and Marek Mlodzik},
journal = {Nature Communications},
year = {2026},
month = oct,
doi = {10.1038/s41467-026-78357-4},
url = {https://www.nature.com/articles/s41467-026-78357-4},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - The Wnt co-receptor Arrow-LRP5/6 is required for planar cell polarity establishment in Drosophila
AU - Ursula Weber
AU - Reza Farhadifar
AU - Marek Mlodzik
PY - 2026
DA - 2026/10/07
JO - Nature Communications
DO - 10.1038/s41467-026-78357-4
UR - https://www.nature.com/articles/s41467-026-78357-4
AB - 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. Current models for Wnt/PCP signaling omit Arr-LRP5/6 and PCP is presumed functioning without these co-receptors. Here we show that arr-LRP5/6 is fully required in Wnt/PCP signaling. In Drosophila, loss of arr results in aberrant PCP mediated cellular orientation and loss of polarity coordination in wings, comparable to core PCP factors mutations, with defects manifest as loss of asymmetric PCP factor localization and reduced levels of Dishevelled (Dsh) with centrally forming wing hairs. In the eye, arr mutant tissue displays phenotypes with defects in chirality and photoreceptors R3 and R4 cell fates. Functional interactions indicate that Fz can recruit Arr, and Arr potentiates Fz-Dsh PCP signaling in all tissues tested. Furthermore, arr-LRP5/6 sensitizes the ligand pair Wg, Wnt4 with the receptor fz, and the core PCP factors fmi and Vang/stbm to cause PCP defects in heterozygous conditions. Our data support a core PCP function of Arr-LRP5/6, promoting Wnt/Fz-Dsh PCP-complex activity.
SN - 2041-1723
ER -