Biol Open. 2021 Dec 1;10(12):bio058892. doi: 10.1242/bio.058892. Epub 2021 Dec 2.
Julien Marcetteau 1, Tamàs Matusek 1, Frédéric Luton 2, Pascal P Thérond 1
1 Université Côte d’Azur; UMR7277 CNRS; Inserm 1091; Institut de Biologie de Valrose (iBV); Parc Valrose, 06108 Nice cedex 2, Nice, France.
2 Université Côte d’Azur; UMR7275 CNRS; Institut de Pharmacologie Moléculaire et Cellulaire (IPMC), 660 Route des Lucioles, Sophia Antipolis, 06560 Valbonne, France.
Wnt signalling is a core pathway involved in a wide range of developmental processes throughout the metazoa. In vitro studies have suggested that the small GTP binding protein Arf6 regulates upstream steps of Wnt transduction, by promoting the phosphorylation of the Wnt co-receptor, LRP6, and the release of β-catenin from the adherens junctions. To assess the relevance of these previous findings in vivo, we analysed the consequence of the absence of Arf6 activity on Drosophila wing patterning, a developmental model of Wnt/Wingless signalling. We observed a dominant loss of wing margin bristles and Senseless expression in Arf6 mutant flies, phenotypes characteristic of a defect in high level Wingless signalling. In contrast to previous findings, we show that Arf6 is required downstream of Armadillo/β-catenin stabilisation in Wingless signal transduction. Our data suggest that Arf6 modulates the activity of a downstream nuclear regulator of Pangolin activity in order to control the induction of high level Wingless signalling. Our findings represent a novel regulatory role for Arf6 in Wingless signalling.