cGMP signalling in a transporting epithelium

2006 ◽  
Vol 34 (4) ◽  
pp. 512-514 ◽  
Author(s):  
S.-A. Davies ◽  
J.P. Day
Keyword(s):  
Drosophila Melanogaster ◽  
Recent Progress ◽  
Renal Tubule ◽  
Genetic Model ◽  
Model Organisms ◽  
Cgmp Signalling

The biochemical aspects of cGMP signalling are well known, although in vivo roles of cGMP have only been recently discovered through work in genetic model organisms. The Drosophila melanogaster Malpighian (renal) tubule has been used to address the roles of cGMP in epithelial function. Here, we describe some of this work and outline recent progress in understanding the organotypic function of novel phosphodiesterases encoded by the D. melanogaster genome.

scholarly journals The Neurotransmitters Involved in Drosophila Alcohol-Induced Behaviors

2020 ◽  
Vol 14 ◽  
Author(s):  
Maggie M. Chvilicek ◽  
Iris Titos ◽  
Adrian Rothenfluh
Keyword(s):  
Drosophila Melanogaster ◽  
Behavioral Response ◽  
Recent Progress ◽  
Mammalian Species ◽  
Health And Safety ◽  
Model Organisms ◽  
Negative Consequences ◽  
Behavioral Repertoire ◽  
Significant Research ◽  
Alcohol Response

Alcohol is a widely used and abused substance with numerous negative consequences for human health and safety. Historically, alcohol's widespread, non-specific neurobiological effects have made it a challenge to study in humans. Therefore, model organisms are a critical tool for unraveling the mechanisms of alcohol action and subsequent effects on behavior. Drosophila melanogaster is genetically tractable and displays a vast behavioral repertoire, making it a particularly good candidate for examining the neurobiology of alcohol responses. In addition to being experimentally amenable, Drosophila have high face and mechanistic validity: their alcohol-related behaviors are remarkably consistent with humans and other mammalian species, and they share numerous conserved neurotransmitters and signaling pathways. Flies have a long history in alcohol research, which has been enhanced in recent years by the development of tools that allow for manipulating individual Drosophila neurotransmitters. Through advancements such as the GAL4/UAS system and CRISPR/Cas9 mutagenesis, investigation of specific neurotransmitters in small subsets of neurons has become ever more achievable. In this review, we describe recent progress in understanding the contribution of seven neurotransmitters to fly behavior, focusing on their roles in alcohol response: dopamine, octopamine, tyramine, serotonin, glutamate, GABA, and acetylcholine. We chose these small-molecule neurotransmitters due to their conservation in mammals and their importance for behavior. While neurotransmitters like dopamine and octopamine have received significant research emphasis regarding their contributions to behavior, others, like glutamate, GABA, and acetylcholine, remain relatively unexplored. Here, we summarize recent genetic and behavioral findings concerning these seven neurotransmitters and their roles in the behavioral response to alcohol, highlighting the fitness of the fly as a model for human alcohol use.

scholarly journals The Intestine of Drosophila melanogaster: An Emerging Versatile Model System to Study Intestinal Epithelial Homeostasis and Host-Microbial Interactions in Humans

2019 ◽  
Vol 7 (9) ◽  
pp. 336 ◽  
Author(s):  
Florence Capo ◽  
Alexa Wilson ◽  
Francesca Di Cara
Keyword(s):  
Drosophila Melanogaster ◽  
Genetic Model ◽  
Current Knowledge ◽  
Cell Lineage ◽  
Model Organism ◽  
Model System ◽  
Microbial Interactions ◽  
Stem Cell Lineage ◽  
Bowel Diseases

In all metazoans, the intestinal tract is an essential organ to integrate nutritional signaling, hormonal cues and immunometabolic networks. The dysregulation of intestinal epithelium functions can impact organism physiology and, in humans, leads to devastating and complex diseases, such as inflammatory bowel diseases, intestinal cancers, and obesity. Two decades ago, the discovery of an immune response in the intestine of the genetic model system, Drosophila melanogaster, sparked interest in using this model organism to dissect the mechanisms that govern gut (patho) physiology in humans. In 2007, the finding of the intestinal stem cell lineage, followed by the development of tools available for its manipulation in vivo, helped to elucidate the structural organization and functions of the fly intestine and its similarity with mammalian gastrointestinal systems. To date, studies of the Drosophila gut have already helped to shed light on a broad range of biological questions regarding stem cells and their niches, interorgan communication, immunity and immunometabolism, making the Drosophila a promising model organism for human enteric studies. This review summarizes our current knowledge of the structure and functions of the Drosophila melanogaster intestine, asserting its validity as an emerging model system to study gut physiology, regeneration, immune defenses and host-microbiota interactions.

scholarly journals In vivo super-resolution RESOLFT microscopy of Drosophila melanogaster

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Sebastian Schnorrenberg ◽  
Tim Grotjohann ◽  
Gerd Vorbrüggen ◽  
Alf Herzig ◽  
Stefan W Hell ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Fluorescent Protein ◽  
Single Cells ◽  
Super Resolution ◽  
Time Lapse ◽  
Live Cell ◽  
Model Organisms ◽  
Alpha Tubulin ◽  
Light Levels

Despite remarkable developments in diffraction unlimited super-resolution microscopy, in vivo nanoscopy of tissues and model organisms is still not satisfactorily established and rarely realized. RESOLFT nanoscopy is particularly suited for live cell imaging because it requires relatively low light levels to overcome the diffraction barrier. Previously, we introduced the reversibly switchable fluorescent protein rsEGFP2, which facilitated fast RESOLFT nanoscopy (<xref ref-type="bibr" rid="bib10">Grotjohann et al., 2012</xref>). In that study, as in most other nanoscopy studies, only cultivated single cells were analyzed. Here, we report on the use of rsEGFP2 for live-cell RESOLFT nanoscopy of sub-cellular structures of intact Drosophila melanogaster larvae and of resected tissues. We generated flies expressing fusion proteins of alpha-tubulin and rsEGFP2 highlighting the microtubule cytoskeleton in all cells. By focusing through the intact larval cuticle, we achieved lateral resolution of <60 nm. RESOLFT nanoscopy enabled time-lapse recordings comprising 40 images and facilitated recordings 40 µm deep within fly tissues.

scholarly journals Inhalation of marijuana affects Drosophila heart function

2018 ◽  
Author(s):  
IM Gómez ◽  
MA Rodríguez ◽  
M Santalla ◽  
G Kassis ◽  
JE Colman Lerner ◽  
...  
Keyword(s):  
Heart Rate ◽  
Drosophila Melanogaster ◽  
Side Effects ◽  
Cardiac Function ◽  
Chronic Exposure ◽  
Genetic Model ◽  
Heart Function ◽  
Scientific Evidence ◽  
Calcium Handling

AbstractMedical uses of marijuana have been recently approved in many countries, and after a long ban on research, there is despicable scientific evidence regarding its action and side effects. We investigated the effect of inhalation of vaporized marijuana on cardiac function in Drosophila melanogaster, a suitable genetic model for assessing cardiovascular function. Chronic exposure of adult flies to vaporized marijuana reduces heart rate, increments contractility and prolongs relaxation. These changes are manifested in the cardiomyocytes with no effect in calcium handling, and in the absence of the canonical cannabinoids receptors identified in mammals. Our results are the first evidence of the in vivo impact of phytocannabinoids in D. melanogaster and open new paths for genetic screenings using vaporized compounds, providing a simple and affordable platform prior to mammalian models.

scholarly journals Modeling Neurodegenerative Disorders in Drosophila melanogaster

2020 ◽  
Vol 21 (9) ◽  
pp. 3055 ◽  
Author(s):  
Harris Bolus ◽  
Kassi Crocker ◽  
Grace Boekhoff-Falk ◽  
Stanislava Chtarbanova
Keyword(s):  
Drosophila Melanogaster ◽  
Neurodegenerative Disorders ◽  
Recent Progress ◽  
Molecular Mechanisms ◽  
Genetic Model ◽  
Model System ◽  
Neural Regeneration ◽  
Future Treatments ◽  
Lateral Sclerosis ◽  
Drosophila Models

Drosophila melanogaster provides a powerful genetic model system in which to investigate the molecular mechanisms underlying neurodegenerative diseases. In this review, we discuss recent progress in Drosophila modeling Alzheimer’s Disease, Parkinson’s Disease, Amyotrophic Lateral Sclerosis (ALS), Huntington’s Disease, Ataxia Telangiectasia, and neurodegeneration related to mitochondrial dysfunction or traumatic brain injury. We close by discussing recent progress using Drosophila models of neural regeneration and how these are likely to provide critical insights into future treatments for neurodegenerative disorders.

scholarly journals Rest is Required to Learn an Appetitively-Reinforced Operant Task in Drosophila

2020 ◽  
Author(s):  
Timothy D. Wiggin ◽  
Yung-Yi Hsiao ◽  
Jeffrey B. Liu ◽  
Robert Huber ◽  
Leslie C. Griffith
Keyword(s):  
Drosophila Melanogaster ◽  
Operant Conditioning ◽  
Food Reward ◽  
Molecular Mechanisms ◽  
Genetic Model ◽  
Fruit Fly ◽  
Model Organisms ◽  
Neural Basis ◽  
Operant Task ◽  
Insight Into

ABSTRACTMaladaptive operant conditioning contributes to development of neuropsychiatric disorders. Candidate genes have been identified that contribute to this maladaptive plasticity, but the neural basis of operant conditioning in genetic model organisms remains poorly understood. The fruit fly Drosophila melanogaster is a versatile genetic model organism that readily forms operant associations with punishment stimuli. However, operant conditioning with a food reward has not been demonstrated in flies, limiting the types of neural circuits that can be studied. Here we present the first sucrose-reinforced operant conditioning paradigm for flies. Flies of both sexes walk along a Y-shaped track with reward locations at the terminus of each hallway. When flies turn in the reinforced direction at the center of the track, sucrose is presented at the end of the hallway. Only flies that rest during training show evidence of learning the reward contingency. Flies rewarded independently of their behavior do not form a learned association but have the same amount of rest as trained flies, showing that rest is not driven by learning. Optogenetically-induced rest does not promote learning, indicating that rest is not sufficient for learning the operant task. We validated the sensitivity of this assay to detect the effect of genetic manipulations by testing the classic learning mutant dunce. Dunce flies are learning impaired in the Y-Track task, indicating a likely role for cAMP in the operant coincidence detector. This novel training paradigm will provide valuable insight into the molecular mechanisms of disease and the link between sleep and learning.SIGNIFICANCE STATEMENTOperant conditioning and mental health are deeply intertwined: maladaptive conditioning contributes to many pathologies, while therapeutic operant conditioning is a frequently used tool in talk therapy. Unlike drug interventions which target molecules or mechanisms, it is not known how operant conditioning changes the brain to promote wellness or distress. To gain mechanistic insight into how this form of learning works, we developed a novel operant training task for the fruit fly Drosophila melanogaster. We made three key discoveries. First, flies are able to learn an operant task to find food reward. Second, rest during training is necessary for learning. Third, the dunce gene is necessary for both classical and operant conditioning in flies, indicating that they may share molecular mechanisms.

scholarly journals Functional enhancer elements drive subclass-selective expression from mouse to primate neocortex

2019 ◽  
Author(s):  
John K. Mich ◽  
Lucas T. Graybuck ◽  
Erik E. Hess ◽  
Joseph T. Mahoney ◽  
Yoshiko Kojima ◽  
...  
Keyword(s):  
Genetic Model ◽  
Ex Vivo ◽  
Cell Types ◽  
Brain Cell ◽  
Model Organisms ◽  
Marker Genes ◽  
Cellular Marker ◽  
Cellular Specificity

SummaryViral genetic tools to target specific brain cell types in humans and non-genetic model organisms will transform basic neuroscience and targeted gene therapy. Here we used comparative epigenetics to identify thousands of human neuronal subclass-specific putative enhancers to regulate viral tools, and 34% of these were conserved in mouse. We established an AAV platform to evaluate cellular specificity of functional enhancers by multiplexed fluorescent in situ hybridization (FISH) and single cell RNA sequencing. Initial testing in mouse neocortex yields a functional enhancer discovery success rate of over 30%. We identify enhancers with specificity for excitatory and inhibitory classes and subclasses including PVALB, LAMP5, and VIP/LAMP5 cells, some of which maintain specificity in vivo or ex vivo in monkey and human neocortex. Finally, functional enhancers can be proximal or distal to cellular marker genes, conserved or divergent across species, and could yield brain-wide specificity greater than the most selective marker genes.

scholarly journals Imaging in vivo Neuronal Transport in Genetic Model Organisms Using Microfluidic Devices

Traffic ◽  
2011 ◽  
Vol 12 (4) ◽  
pp. 372-385 ◽  
Author(s):  
Sudip Mondal ◽  
Shikha Ahlawat ◽  
Kaustubh Rau ◽  
V. Venkataraman ◽  
Sandhya P. Koushika
Keyword(s):  
Genetic Model ◽  
Microfluidic Devices ◽  
Model Organisms ◽  
Neuronal Transport
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