Wnt Signaling Rescues Amyloid Beta-Induced Gut Stem Cell Loss

Wnt signaling has well established roles in development and cancer progression. Its roles during normal adult homeostasis are less well studied, but Wnt is a major stem cell regulating factor in adult tissues. Here we use an optogenetic model of amyloid beta aggregation to examine the effect of Wnt signaling on protein aggregation. We observe that Wnt activation rescues the detrimental effects of Amyloid. We analyze the gene expression changes downstream of Wnt that contribute to this rescue and find a protein misfolding response and a metabolic response, but the major factor we focus on is inflammation. Wnt expression reduces inflammation through repression of Toll activating factors, and chronic Toll activation reduces lifespan. We propose that the protective effect observed for lithium treatment functions at least in part through Wnt activation and inhibition of inflammation. Overall design: Drosophila midgut RNA profiles of wild type (WT), Wg, Aß-CRY2-mCh + Wg, and Aß-CRY2-mCh exposed to light.