Wnt ligands secreted by subepithelial mesenchymal cells are essential for the survival of intestinal stem cells and gut homeostasis

Valenta, Tomas; Degirmenci, Bahar; Moor, Andreas E; Herr, Patrick; Zimmerli, Dario; Moor, Matthias B; Hausmann, George; Cantù, Claudio; Aguet, Michel; Basler, Konrad

doi:10.1016/j.celrep.2016.03.088

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Valenta, T., Degirmenci, B., Moor, A. E., Herr, P., Zimmerli, D., Moor, M. B., Hausmann, G., Cantù, C., Aguet, M., & Basler, K. (2016). Wnt ligands secreted by subepithelial mesenchymal cells are essential for the survival of intestinal stem cells and gut homeostasis. Cell Reports, 15, 1–8. https://doi.org/10.1016/j.celrep.2016.03.088

Abstract

Targeting of Wnt signaling represents a promising anti-cancer therapy. However, the consequences of systemically attenuating the Wnt pathway in an adult organism are unknown. Here, we globally prevent Wnt secretion by genetically ablating Wntless. We find that preventing Wnt signaling in the entire body causes mortality due to impaired intestinal homeostasis. This is caused by the loss of intestinal stem cells. Reconstitution of Wnt/β-catenin signaling via delivery of external Wnt ligands prolongs the survival of intestinal stem cells