Wnt/β-catenin signaling within multiple cell types dependent upon kramer regulates Drosophila intestinal stem cell proliferation
Hongyan Sun,
Adnan Shami Shah,
Din-Chi Chiu,
Alessandro Bonfini,
Nicolas Buchon,
Jeremy M. Baskin
Affiliations
Hongyan Sun
Weill Institute for Cell & Molecular Biology, Cornell University, Ithaca, NY 14853, USA
Adnan Shami Shah
Weill Institute for Cell & Molecular Biology, Cornell University, Ithaca, NY 14853, USA; Department of Chemistry & Chemical Biology, Cornell University, Ithaca, NY 14853, USA
Din-Chi Chiu
Weill Institute for Cell & Molecular Biology, Cornell University, Ithaca, NY 14853, USA; Department of Chemistry & Chemical Biology, Cornell University, Ithaca, NY 14853, USA
Alessandro Bonfini
Cornell Institute of Host Microbe Interactions and Disease, Department of Entomology, Cornell University, Ithaca, NY 14853, USA; Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Zhejiang University, Haining 314400, P.R. China; Edinburgh Medical School: Biomedical Sciences, College of Medicine and Veterinary Medicine, The University of Edinburgh, Edinburgh, UK
Nicolas Buchon
Cornell Institute of Host Microbe Interactions and Disease, Department of Entomology, Cornell University, Ithaca, NY 14853, USA
Jeremy M. Baskin
Weill Institute for Cell & Molecular Biology, Cornell University, Ithaca, NY 14853, USA; Department of Chemistry & Chemical Biology, Cornell University, Ithaca, NY 14853, USA; Corresponding author
Summary: The 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 the Drosophila midgut with a non-lethal enteric pathogen, we examine the cellular determinants of ISC proliferation, harnessing kramer, 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 that kramer regulates Wnt signaling in this context by antagonizing kelch, a Cullin-3 E3 ligase adaptor that mediates Dishevelled polyubiquitination. This work establishes kramer as 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.
