Enteroendocrine Cells Support Intestinal Stem-Cell-Mediated Homeostasis in Drosophila

Summary: Intestinal stem cells in the adult Drosophila midgut are regulated by growth factors produced from the surrounding niche cells including enterocytes and visceral muscle. The role of the other major cell type, the secretory enteroendocrine cells, in regulating intestinal stem cells remains u...

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Main Authors: Alla Amcheslavsky, Wei Song, Qi Li, Yingchao Nie, Ivan Bragatto, Dominique Ferrandon, Norbert Perrimon, Y. Tony Ip
Format: Article
Language:English
Published: Elsevier 2014-10-01
Series:Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124714007281
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author Alla Amcheslavsky
Wei Song
Qi Li
Yingchao Nie
Ivan Bragatto
Dominique Ferrandon
Norbert Perrimon
Y. Tony Ip
author_facet Alla Amcheslavsky
Wei Song
Qi Li
Yingchao Nie
Ivan Bragatto
Dominique Ferrandon
Norbert Perrimon
Y. Tony Ip
author_sort Alla Amcheslavsky
collection DOAJ
description Summary: Intestinal stem cells in the adult Drosophila midgut are regulated by growth factors produced from the surrounding niche cells including enterocytes and visceral muscle. The role of the other major cell type, the secretory enteroendocrine cells, in regulating intestinal stem cells remains unclear. We show here that newly eclosed scute loss-of-function mutant flies are completely devoid of enteroendocrine cells. These enteroendocrine cell-less flies have normal ingestion and fecundity but shorter lifespan. Moreover, in these newly eclosed mutant flies, the diet-stimulated midgut growth that depends on the insulin-like peptide 3 expression in the surrounding muscle is defective. The depletion of Tachykinin-producing enteroendocrine cells or knockdown of Tachykinin leads to a similar although less severe phenotype. These results establish that enteroendocrine cells serve as an important link between diet and visceral muscle expression of an insulin-like growth factor to stimulate intestinal stem cell proliferation and tissue growth. : Amcheslavsky et al. show that enteroendocrine cells serve a niche function to regulate intestinal stem cell division. High-nutrient diet stimulates intestinal stem cell division and intestinal tissue growth in newly eclosed flies. Enteroendocrine cells act as an important link for this process by producing gut hormones such as Tachykinin to regulate the expression of an insulin-like peptide DILP3 in the visceral muscle. This Drosophila model helps to elucidate the function of enteroendocrine cells in complex whole-animal physiology.
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spelling doaj.art-3c6317ccd6574b5dba070e3a1766982f2022-12-21T19:27:32ZengElsevierCell Reports2211-12472014-10-01913239Enteroendocrine Cells Support Intestinal Stem-Cell-Mediated Homeostasis in DrosophilaAlla Amcheslavsky0Wei Song1Qi Li2Yingchao Nie3Ivan Bragatto4Dominique Ferrandon5Norbert Perrimon6Y. Tony Ip7Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USAHoward Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA; Department of Genetics,Harvard Medical School, Boston, MA 02115, USAProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USAProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USAUnité Propre de Recherche 9022 du Centre National de la Recherche Scientifique, University of Strasbourg Institute for Advanced Study, Institut de Biologie Moléculaire et Cellulaire, 67084 Strasbourg Cedex, FranceUnité Propre de Recherche 9022 du Centre National de la Recherche Scientifique, University of Strasbourg Institute for Advanced Study, Institut de Biologie Moléculaire et Cellulaire, 67084 Strasbourg Cedex, FranceHoward Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA; Department of Genetics,Harvard Medical School, Boston, MA 02115, USAProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA; Corresponding authorSummary: Intestinal stem cells in the adult Drosophila midgut are regulated by growth factors produced from the surrounding niche cells including enterocytes and visceral muscle. The role of the other major cell type, the secretory enteroendocrine cells, in regulating intestinal stem cells remains unclear. We show here that newly eclosed scute loss-of-function mutant flies are completely devoid of enteroendocrine cells. These enteroendocrine cell-less flies have normal ingestion and fecundity but shorter lifespan. Moreover, in these newly eclosed mutant flies, the diet-stimulated midgut growth that depends on the insulin-like peptide 3 expression in the surrounding muscle is defective. The depletion of Tachykinin-producing enteroendocrine cells or knockdown of Tachykinin leads to a similar although less severe phenotype. These results establish that enteroendocrine cells serve as an important link between diet and visceral muscle expression of an insulin-like growth factor to stimulate intestinal stem cell proliferation and tissue growth. : Amcheslavsky et al. show that enteroendocrine cells serve a niche function to regulate intestinal stem cell division. High-nutrient diet stimulates intestinal stem cell division and intestinal tissue growth in newly eclosed flies. Enteroendocrine cells act as an important link for this process by producing gut hormones such as Tachykinin to regulate the expression of an insulin-like peptide DILP3 in the visceral muscle. This Drosophila model helps to elucidate the function of enteroendocrine cells in complex whole-animal physiology.http://www.sciencedirect.com/science/article/pii/S2211124714007281
spellingShingle Alla Amcheslavsky
Wei Song
Qi Li
Yingchao Nie
Ivan Bragatto
Dominique Ferrandon
Norbert Perrimon
Y. Tony Ip
Enteroendocrine Cells Support Intestinal Stem-Cell-Mediated Homeostasis in Drosophila
Cell Reports
title Enteroendocrine Cells Support Intestinal Stem-Cell-Mediated Homeostasis in Drosophila
title_full Enteroendocrine Cells Support Intestinal Stem-Cell-Mediated Homeostasis in Drosophila
title_fullStr Enteroendocrine Cells Support Intestinal Stem-Cell-Mediated Homeostasis in Drosophila
title_full_unstemmed Enteroendocrine Cells Support Intestinal Stem-Cell-Mediated Homeostasis in Drosophila
title_short Enteroendocrine Cells Support Intestinal Stem-Cell-Mediated Homeostasis in Drosophila
title_sort enteroendocrine cells support intestinal stem cell mediated homeostasis in drosophila
url http://www.sciencedirect.com/science/article/pii/S2211124714007281
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