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 First person – Laura Tamberg

2020 ◽  
Vol 13 (7) ◽  
pp. dmm046532
Keyword(s):  
Transcription Factor ◽  
Drosophila Melanogaster ◽  
Molecular Mechanisms ◽  
Model System ◽  
Early Career ◽  
Disease Models ◽  
First Person ◽  
Early Career Researchers ◽  
University Of Technology ◽  
Selection Of

ABSTRACTFirst Person is a series of interviews with the first authors of a selection of papers published in Disease Models & Mechanisms, helping early-career researchers promote themselves alongside their papers. Laura Tamberg is first author on ‘Daughterless, the Drosophila orthologue of TCF4, is required for associative learning and maintenance of the synaptic proteome’, published in DMM. Laura is a PhD student in the lab of Tõnis Timmusk at the Tallinn University of Technology, Tallinn, Estonia. Her research involves investigating the use of Drosophila melanogaster as a model system to understand the molecular mechanisms underlying transcription factor TCF4-related neuronal diseases.

scholarly journals Tau Accumulation via Reduced BAG3-mediated Autophagy Is Required for GGGGCC Repeat Expansion-Induced Neurodegeneration

2019 ◽  
Author(s):  
Xue Wen ◽  
Ping An ◽  
Hexuan Li ◽  
Zijian Zhou ◽  
Yimin Sun ◽  
...  
Keyword(s):  
Tau Protein ◽  
Neurodegenerative Disorders ◽  
Motor Performance ◽  
Molecular Mechanisms ◽  
Repeat Expansion ◽  
Cag Repeats ◽  
Reduced Activity ◽  
Lateral Sclerosis

SUMMARYExpansions of trinucleotide or hexanucleotide repeats lead to several neurodegenerative disorders including Huntington disease (HD, caused by the expanded CAG repeats (CAGr) in the HTT gene) and amyotrophic lateral sclerosis (ALS, could be caused by the expanded GGGGCC repeats (G4C2r) in the C9ORF72 gene), of which the molecular mechanisms remain unclear. Here we demonstrate that loss of the Drosophila orthologue of tau protein (dtau) significantly rescued in vivo neurodegeneration, motor performance impairments, and shortened life-span in Drosophila models expressing mutant HTT protein with expanded CAGr or the expanded G4C2r. Importantly, expression of human tau (htau4R) restored the disease-relevant phenotypes that were mitigated by the loss of dtau, suggesting a conserved role of tau in neurodegeneration. We further discovered that G4C2r expression increased dtau accumulation, possibly due to reduced activity of BAG3-mediated autophagy. Our study reveals a conserved role of tau in G4C2r-induced neurotoxicity in Drosophila models, providing mechanistic insights and potential therapeutic targets.

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 The Fruit Fly Drosophila melanogaster as a Model System to Study Cholesterol Metabolism and Homeostasis

Cholesterol ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Ryusuke Niwa ◽  
Yuko S. Niwa
Keyword(s):  
Drosophila Melanogaster ◽  
Steroid Hormones ◽  
Molecular Mechanisms ◽  
Cholesterol Metabolism ◽  
Cholesterol Biosynthesis ◽  
Fruit Fly ◽  
Model System ◽  
Biophysical Properties ◽  
Type C ◽  
Niemann Pick

Cholesterol has long been recognized for its versatile roles in influencing the biophysical properties of cell membranes and for serving as a precursor of steroid hormones. While many aspects of cholesterol biosynthesis are well understood, little is currently known about the molecular mechanisms of cholesterol metabolism and homeostasis. Recently, genetic approaches in the fruit fly, Drosophila melanogaster, have been successfully used for the analysis of molecular mechanisms that regulate cholesterol metabolism and homeostasis. This paper summarizes the recent studies on genes that regulate cholesterol metabolism and homeostasis, including neverland, Niemann Pick type C(NPC) disease genes, and DHR96.

scholarly journals Drosophila melanogaster: A Veritable Genetic Tool and in vivo Model for Human Alzheimer’s Disease

2019 ◽  
pp. 1-9
Author(s):  
Oluwatosin Imoleayo, Oyeniran
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Drosophila Melanogaster ◽  
Molecular Mechanisms ◽  
Fruit Fly ◽  
Human Diseases ◽  
Model Organisms ◽  
In Vivo Model ◽  
Brain Functions ◽  
Drosophila Models

The rise in the cases of neurodegenerative diseases, such as the familial forms of Alzheimer’s disease is worrisome and a burden to many societies in our ever-increasing world. Due to the complexity in the nature of the brain and spinal cord characterized by an extremely organized network of neuronal cells, there is a need to answer scientific inquiries in uncomplicated, though similar, systems. Drosophila melanogaster (fruit-fly) is a well-studied and easily managed genetic model organism used for discerning the molecular mechanisms of many human diseases. There are strong conservations of several basic biological, physiological and neurological features between D. melanogaster and mammals, as about 75% of all human disease-causing genes are considered to possess a functional homolog in the fruit-fly. The development of Drosophila models of several neurodegenerative disorders via developed transgenic technologies has presented spectacular similarities to human diseases. An advantage that the fruit-fly has over other model organisms, such as the mouse, is its comparatively brief lifespan, which allows complex inquiries about brain functions to be addressed more quickly. Furthermore, there have been steady increases in understanding the pathophysiological basis of many neurological disorders via genetic screenings with the aid of Drosophila models. This review presents a widespread summary of the fruit-fly models relevant to Alzheimer’s disease, and highlight important genetic modifiers that have been recognized using this model.

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 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 Modeling dietary influences on offspring metabolic programming in Drosophila melanogaster

Reproduction ◽  
2016 ◽  
pp. R79-R90 ◽  
Author(s):  
Rita T Brookheart ◽  
Jennifer G Duncan
Keyword(s):  
Drosophila Melanogaster ◽  
Childhood Obesity ◽  
Molecular Mechanisms ◽  
Genetic Model ◽  
Model Organism ◽  
Metabolic Programming ◽  
Present Evidence

The influence of nutrition on offspring metabolism has become a hot topic in recent years owing to the growing prevalence of maternal and childhood obesity. Studies in mammals have identified several factors correlating with parental and early offspring dietary influences on progeny health; however, the molecular mechanisms that underlie these factors remain undiscovered. Mammalian metabolic tissues and pathways are heavily conserved inDrosophila melanogaster, making the fly an invaluable genetic model organism for studying metabolism. In this review, we discuss the metabolic similarities between mammals andDrosophilaand present evidence supporting its use as an emerging model of metabolic programming.

scholarly journals Exploiting the Fruitfly, Drosophila melanogaster, to Identify the Molecular Basis of Cryptochrome-Dependent Magnetosensitivity

2021 ◽  
Vol 3 (1) ◽  
pp. 127-136
Author(s):  
Adam Bradlaugh ◽  
Anna L. Munro ◽  
Alex R. Jones ◽  
Richard A. Baines
Keyword(s):  
Drosophila Melanogaster ◽  
Molecular Basis ◽  
Genetic Model ◽  
Radical Pair ◽  
Quantum Effect ◽  
Fruit Fly ◽  
Test Tube ◽  
Model System ◽  
Significant Progress ◽  
Made In

The flavoprotein CRYPTOCHROME (CRY) is now generally believed to be a magnetosensor, providing geomagnetic information via a quantum effect on a light-initiated radical pair reaction. Whilst there is considerable physical and behavioural data to support this view, the precise molecular basis of animal magnetosensitivity remains frustratingly unknown. A key reason for this is the difficulty in combining molecular and behavioural biological experiments with the sciences of magnetics and spin chemistry. In this review, we highlight work that has utilised the fruit fly, Drosophila melanogaster, which provides a highly tractable genetic model system that offers many advantages for the study of magnetosensitivity. Using this “living test-tube”, significant progress has been made in elucidating the molecular basis of CRY-dependent magnetosensitivity.

Sign in / Sign up

Export Citation Format

Share Document