Local control of intestinal stem cell homeostasis by enteroendocrine cells in the adult Drosophila midgut

Scopelliti, A., Cordero, J. B., Diao, F., Strathdee, K., White, B. H., Sansom, O. J. and Vidal, M. (2014) Local control of intestinal stem cell homeostasis by enteroendocrine cells in the adult Drosophila midgut. Current Biology, 24(11), pp. 1199-1211. (doi:10.1016/j.cub.2014.04.007)

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Publisher's URL: http://dx.doi.org/10.1016/j.cub.2014.04.007

Abstract

Background: Enteroendocrine cells populate gastrointestinal tissues and are known to translate local cues into systemic responses through the release of hormones into the bloodstream.<p></p> Results: Here we report a novel function of enteroendocrine cells acting as local regulators of intestinal stem cell (ISC) proliferation through modulation of the mesenchymal stem cell niche in the <i>Drosophila</i> midgut. This paracrine signaling acts to constrain ISC proliferation within the epithelial compartment. Mechanistically, midgut enteroendocrine cells secrete the neuroendocrine hormone Bursicon, which acts—beyond its known roles in development—as a paracrine factor on the visceral muscle (VM). Bursicon binding to its receptor, DLGR2, the ortholog of mammalian leucine-rich repeat-containing G protein-coupled receptors (LGR4-6), represses the production of the VM-derived EGF-like growth factor Vein through activation of cAMP.<p></p> Conclusions: We therefore identify a novel paradigm in the regulation of ISC quiescence involving the conserved ligand/receptor Bursicon/DLGR2 and a previously unrecognized tissue-intrinsic role of enteroendocrine cells.<p></p>

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Vidal, Dr Marcos and Strathdee, Mrs Karen and Cordero, Dr Julia and Sansom, Professor Owen and Scopelliti, Mr Alessandro
Authors: Scopelliti, A., Cordero, J. B., Diao, F., Strathdee, K., White, B. H., Sansom, O. J., and Vidal, M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Current Biology
Publisher:Cell Press
ISSN:0960-9822
ISSN (Online):1879-0445
Copyright Holders:Copyright © 2014 The Authors
First Published:First published in Current Biology 24(11):1199-1211
Publisher Policy:Reproduced under a Creative Commons License

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