Abstract
ABSTRACTThe gut epithelium is subject to constant renewal, a process reliant upon intestinal stem cell (ISC) proliferation that is driven by Wnt/β-catenin signaling. Despite the importance of Wnt signaling within ISCs, the relevance of Wnt signaling within other gut cell types and the underlying mechanisms that modulate Wnt signaling in these contexts remain incompletely understood. Using challenge of theDrosophilamidgut with a non-lethal enteric pathogen, we examine the cellular determinants of ISC proliferation, harnessingkramer, a recently identified regulator of Wnt signaling pathways, as a mechanistic tool. We find that Wnt signaling within Prospero-positive cells supports ISC proliferation and thatkramerregulates Wnt signaling in this context by antagonizingkelch, a Cullin-3 E3 ligase adaptor that mediates Dishevelled polyubiquitination. This work establisheskrameras a physiological regulator of Wnt/β-catenin signaling in vivo and suggests enteroendocrine cells as a new cell type that regulates ISC proliferation via Wnt/β-catenin signaling.
Publisher
Cold Spring Harbor Laboratory