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      Physiology, Development, and Disease Modeling in the Drosophila Excretory System

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          Abstract

          The insect excretory system contains two organ systems acting in concert: the Malpighian tubules and the hindgut perform essential roles in excretion and ionic and osmotic homeostasis. For over 350 years, these two organs have fascinated biologists as a model of organ structure and function. As part of a recent surge in interest, research on the Malpighian tubules and hindgut of Drosophila have uncovered important paradigms of organ physiology and development. Further, many human disease processes can be modeled in these organs. Here, focusing on discoveries in the past 10 years, we provide an overview of the anatomy and physiology of the Drosophila excretory system. We describe the major developmental events that build these organs during embryogenesis, remodel them during metamorphosis, and repair them following injury. Finally, we highlight the use of the Malpighian tubules and hindgut as accessible models of human disease biology. The Malpighian tubule is a particularly excellent model to study rapid fluid transport, neuroendocrine control of renal function, and modeling of numerous human renal conditions such as kidney stones, while the hindgut provides an outstanding model for processes such as the role of cell chirality in development, nonstem cell–based injury repair, cancer-promoting processes, and communication between the intestine and nervous system.

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          Most cited references309

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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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            Chronic kidney disease and mortality risk: a systematic review.

            Current guidelines identify people with chronic kidney disease (CKD) as being at high risk for cardiovascular and all-cause mortality. Because as many as 19 million Americans may have CKD, a comprehensive summary of this risk would be potentially useful for planning public health policy. A systematic review of the association between non-dialysis-dependent CKD and the risk for all-cause and cardiovascular mortality was conducted. Patient- and study-related characteristics that influenced the magnitude of these associations also were investigated. MEDLINE and EMBASE databases were searched, and reference lists through December 2004 were consulted. Authors of 10 primary studies provided additional data. Cohort studies or cohort analyses of randomized, controlled trials that compared mortality between those with and without chronically reduced kidney function were included. Studies were excluded from review when participants were followed for < 1 yr or had ESRD. Two reviewers independently extracted data on study setting, quality, participant and renal function characteristics, and outcomes. Thirty-nine studies that followed a total of 1,371,990 participants were reviewed. The unadjusted relative risk for mortality in participants with reduced kidney function compared with those without ranged from 0.94 to 5.0 and was significantly more than 1.0 in 93% of cohorts. Among the 16 studies that provided suitable data, the absolute risk for death increased exponentially with decreasing renal function. Fourteen cohorts described the risk for mortality from reduced kidney function, after adjustment for other established risk factors. Although adjusted relative hazards were consistently lower than unadjusted relative risks (median reduction 17%), they remained significantly more than 1.0 in 71% of cohorts. This review supports current guidelines that identify individuals with CKD as being at high risk for cardiovascular mortality. Determining which interventions best offset this risk remains a health priority.
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              Evidence that stem cells reside in the adult Drosophila midgut epithelium.

              Adult stem cells maintain organ systems throughout the course of life and facilitate repair after injury or disease. A fundamental property of stem and progenitor cell division is the capacity to retain a proliferative state or generate differentiated daughter cells; however, little is currently known about signals that regulate the balance between these processes. Here, we characterize a proliferating cellular compartment in the adult Drosophila midgut. Using genetic mosaic analysis we demonstrate that differentiated cells in the epithelium arise from a common lineage. Furthermore, we show that reduction of Notch signalling leads to an increase in the number of midgut progenitor cells, whereas activation of the Notch pathway leads to a decrease in proliferation. Thus, the midgut progenitor's default state is proliferation, which is inhibited through the Notch signalling pathway. The ability to identify, manipulate and genetically trace cell lineages in the midgut should lead to the discovery of additional genes that regulate stem and progenitor cell biology in the gastrointestinal tract.
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                Author and article information

                Journal
                Genetics
                Genetics
                genetics
                genetics
                genetics
                Genetics
                Genetics Society of America
                0016-6731
                1943-2631
                February 2020
                3 February 2020
                3 February 2020
                : 214
                : 2
                : 235-264
                Affiliations
                [* ]Department of Cell Biology, University Medical Center, Durham, North Carolina 27710
                []Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710
                []Institute of Molecular, Cell, and Systems Biology, University of Glasgow, G12 8QQ, United Kingdom
                Author notes
                [1 ]Corresponding authors: Duke University, DUMC Box 3813, C318 LSRC, Durham, NC 27710. E-mail: don.fox@ 123456duke.edu ; and Julian.Dow@ 123456glasgow.ac.uk
                Author information
                http://orcid.org/0000-0003-2390-3707
                http://orcid.org/0000-0001-9026-0559
                http://orcid.org/0000-0002-9595-5146
                http://orcid.org/0000-0002-0436-179X
                Article
                302289
                10.1534/genetics.119.302289
                7017010
                32029579
                1512c607-5880-45fb-9d02-b1ece763825f
                Copyright © 2020 by the Genetics Society of America

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

                History
                : 07 October 2019
                : 04 November 2019
                Page count
                Figures: 3, Tables: 2, Equations: 0, References: 341, Pages: 30
                Categories
                Flybook
                Development and Growth

                Genetics
                colon,drosophila,excretion,hindgut,kidney,large intestine,malpighian tubule,flybook
                Genetics
                colon, drosophila, excretion, hindgut, kidney, large intestine, malpighian tubule, flybook

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