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      Anatomy and Physiology of the Digestive Tract of Drosophila melanogaster

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          Abstract

          The gastrointestinal tract has recently come to the forefront of multiple research fields. It is now recognized as a major source of signals modulating food intake, insulin secretion and energy balance. It is also a key player in immunity and, through its interaction with microbiota, can shape our physiology and behavior in complex and sometimes unexpected ways. The insect intestine had remained, by comparison, relatively unexplored until the identification of adult somatic stem cells in the Drosophila intestine over a decade ago. Since then, a growing scientific community has exploited the genetic amenability of this insect organ in powerful and creative ways. By doing so, we have shed light on a broad range of biological questions revolving around stem cells and their niches, interorgan signaling and immunity. Despite their relatively recent discovery, some of the mechanisms active in the intestine of flies have already been shown to be more widely applicable to other gastrointestinal systems, and may therefore become relevant in the context of human pathologies such as gastrointestinal cancers, aging, or obesity. This review summarizes our current knowledge of both the formation and function of the Drosophila melanogaster digestive tract, with a major focus on its main digestive/absorptive portion: the strikingly adaptable adult midgut.

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          Most cited references388

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          Using FlyAtlas to identify better Drosophila melanogaster models of human disease.

          FlyAtlas, a new online resource, provides the most comprehensive view yet of expression in multiple tissues of Drosophila melanogaster. Meta-analysis of the data shows that a significant fraction of the genome is expressed with great tissue specificity in the adult, demonstrating the need for the functional genomic community to embrace a wide range of functional phenotypes. Well-known developmental genes are often reused in surprising tissues in the adult, suggesting new functions. The homologs of many human genetic disease loci show selective expression in the Drosophila tissues analogous to the affected human tissues, providing a useful filter for potential candidate genes. Additionally, the contributions of each tissue to the whole-fly array signal can be calculated, demonstrating the limitations of whole-organism approaches to functional genomics and allowing modeling of a simple tissue fractionation procedure that should improve detection of weak or tissue-specific signals.
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            Cytokine/Jak/Stat signaling mediates regeneration and homeostasis in the Drosophila midgut.

            Cells in intestinal epithelia turn over rapidly due to damage from digestion and toxins produced by the enteric microbiota. Gut homeostasis is maintained by intestinal stem cells (ISCs) that divide to replenish the intestinal epithelium, but little is known about how ISC division and differentiation are coordinated with epithelial cell loss. We show here that when enterocytes (ECs) in the Drosophila midgut are subjected to apoptosis, enteric infection, or JNK-mediated stress signaling, they produce cytokines (Upd, Upd2, and Upd3) that activate Jak/Stat signaling in ISCs, promoting their rapid division. Upd/Jak/Stat activity also promotes progenitor cell differentiation, in part by stimulating Delta/Notch signaling, and is required for differentiation in both normal and regenerating midguts. Hence, cytokine-mediated feedback enables stem cells to replace spent progeny as they are lost, thereby establishing gut homeostasis.
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              Drosophila microbiome modulates host developmental and metabolic homeostasis via insulin signaling.

              The symbiotic microbiota profoundly affect many aspects of host physiology; however, the molecular mechanisms underlying host-microbe cross-talk are largely unknown. Here, we show that the pyrroloquinoline quinone-dependent alcohol dehydrogenase (PQQ-ADH) activity of a commensal bacterium, Acetobacter pomorum, modulates insulin/insulin-like growth factor signaling (IIS) in Drosophila to regulate host homeostatic programs controlling developmental rate, body size, energy metabolism, and intestinal stem cell activity. Germ-free animals monoassociated with PQQ-ADH mutant bacteria displayed severe deregulation of developmental and metabolic homeostasis. Importantly, these defects were reversed by enhancing host IIS or by supplementing the diet with acetic acid, the metabolic product of PQQ-ADH.
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                Author and article information

                Journal
                Genetics
                Genetics
                genetics
                genetics
                genetics
                Genetics
                Genetics Society of America
                0016-6731
                1943-2631
                October 2018
                1 October 2018
                1 October 2018
                : 210
                : 2
                : 357-396
                Affiliations
                [* ]Medical Research Council London Institute of Medical Sciences, Imperial College London, W12 0NN, United Kingdom
                []Buck Institute for Research on Aging, Novato, California 94945-1400
                []Immunology Discovery, Genentech, Inc., San Francisco, California 94080
                [§ ]Global Health Institute, School of Life Sciences, École polytechnique fédérale de Lausanne, CH-1015 Lausanne, Switzerland
                Author notes
                [1 ]Corresponding author: Level 2, Room 232, ICTEM Bldg., MRC London Institute of Medical Sciences, Hammersmith Campus, Du Cane Rd., London W12 0NN, United Kingdom. E-mail: i.miguel-aliaga@ 123456imperial.ac.uk
                Author information
                http://orcid.org/0000-0002-1082-5108
                Article
                300224
                10.1534/genetics.118.300224
                6216580
                30287514
                2e34e8be-d511-401a-859f-259265733a3f
                Copyright © 2018 Miguel-Aliaga et al.

                Available freely online through the author-supported open access option.

                This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 31 May 2018
                : 26 July 2018
                Page count
                Figures: 5, Tables: 0, Equations: 0, References: 430, Pages: 40
                Categories
                Flybook
                Development and Growth

                Genetics
                flybook,drosophila,intestine,midgut,enteric nervous system,microbiota,immunity,metals,aging,digestion,absorption,enteroendocrine,stem cells

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