title: Local control of intestinal stem cell homeostasis by enteroendocrine cells in the adult Drosophila midgut.
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.
  
  
  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 Drosophila 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.
  
  
  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.
authors.affiliation: The Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Scopelliti
authors.affiliation: The Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK. Electronic address: j.cordero@beatson.gla.ac.uk.
authors.forename: Julia B
authors.initials: JB
authors.lastname: Cordero
authors.affiliation: Laboratory of Molecular Biology, NIMH, 35 Convent Drive, MSC 4035, Bethesda, MD 20892-4035, USA.
authors.forename: Fengqiu
authors.initials: F
authors.lastname: Diao
authors.affiliation: The Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.
authors.forename: Karen
authors.initials: K
authors.lastname: Strathdee
authors.affiliation: Laboratory of Molecular Biology, NIMH, 35 Convent Drive, MSC 4035, Bethesda, MD 20892-4035, USA.
authors.forename: Benjamin H
authors.initials: BH
authors.lastname: White
authors.affiliation: The Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.
authors.forename: Owen J
authors.initials: OJ
authors.lastname: Sansom
authors.affiliation: The Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK. Electronic address: m.vidal@beatson.gla.ac.uk.
authors.forename: Marcos
authors.initials: M
authors.lastname: Vidal
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D000242:Cyclic AMP / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics / Q000502:physiology*; D019858:Enteroendocrine Cells / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation; D006706:Homeostasis; D007422:Intestines / Q000166:cytology / Q000502:physiology; D007447:Invertebrate Hormones / Q000235:genetics / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D009132:Muscles / Q000378:metabolism; D020880:Neuregulins / Q000235:genetics / Q000378:metabolism; D019899:Paracrine Communication; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D007447:Invertebrate Hormones; D020880:Neuregulins; D043562:Receptors, G-Protein-Coupled; C416853:Rk protein, Drosophila; C102104:vn protein, Drosophila; C002295:bursicon; D000242:Cyclic AMP