Actomyosin contractility modulates Wnt signaling through adherens junction stability

Abstract

Mechanical forces can influence the canonical Wnt signaling pathway in processes like mesoderm differentiation and tissue stiffness during tumorigenesis, but a molecular mechanism involving both in a developing epithelium and its homeostasis is lacking. We identified that increased non-muscle myosin II activation and cellular contraction inhibited Wnt target gene transcription in developing Drosophila. Genetic interactions studies identified this effect was due to myosin-induced accumulation of cortical F-actin resulting in clustering and accumulation of E-cadherin to the adherens junctions. E-cadherin titrates any available {beta}-catenin, the Wnt pathway transcriptional co-activator, to the adherens junctions in order to maintain cell-cell adhesion under contraction. We show that decreased levels of cytoplasmic {beta}-catenin result in insufficient nuclear translocation for full Wnt target gene transcription. Our work elucidates a mechanism in which the dynamic activation of actomyosin contractility refines patterning of Wnt transcription during development and maintenance of epithelial tissue in organisms.