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Drosophila: A Versatile Model in Biology and Medicine
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Drosophila: A Versatile Model in Biology and Medicine

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 30 August 2024 | Viewed by 5365

Special Issue Editors

Dr. Maria Grazia Giansanti

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Guest Editor
Istituto di Biologia e Patologia Molecolari del Consiglio Nazionale delle Ricerche, Dipartimento di Biologia e Biotecnologie, Università Sapienza di Roma, Piazzale Aldo Moro 5, 00185 Rome, Italy
Interests: Drosophila melanogaster; Drosophila model; oncoprotein; cytokinesis
Special Issues, Collections and Topics in MDPI journals
Dr. Roberto Piergentili

E-Mail Website
Guest Editor
Istituto di Biologia e Patologia Molecolari del Consiglio Nazionale delle Ricerche (IBPM-CNR), Dipartimento di Biologia e Biotecnologie, Università Sapienza di Roma, Piazzale Aldo Moro 5, 00185 Rome, Italy
Interests: chromatin structure and function; heterochromatin; Drosophila melanogaster; mitosis and male meiosis; cytokinesis; DNA repair; cancer epigenetics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Since the year 1901, thanks to the pioneering work of the entomologist Charles W. Woodworth, Drosophila melanogaster has been pointed out as a highly suitable model organism to study processes that are conserved in all eukaryotic cells. Since then, the fruit fly has been used to study cell proliferation and metabolism, genetics, physiology, microbial pathogenesis, and life history evolution. Indeed, studies on the fruit fly have, to date, been awarded five Nobel Prizes for “Physiology or Medicine” collectively: in 1933, for discovering the role played by chromosomes in heredity (Morgan); in 1946, for the production of mutations by means of X-ray irradiation (Muller); in 1995, for the study of the genetic control of early embryonic development (Lewis, Nüsslein-Volhard, and Wieschaus); in 2011, for understanding how receptors detect microorganisms and activate innate immunity (Hoffmann); and in 2017, for unveiling the molecular mechanisms controlling the circadian rhythm (Hall, Rosbash, and Young). It is currently estimated that about 75% of known human disease genes have a recognizable, functional homologue in fruit flies, including the genes involved in important human pathologies such as Down’s syndrome, Alzheimer’s disease, autism, diabetes, and most—if not all—types of cancer. Drosophila is also a very valuable tool in the study of rare human diseases, where developing vertebrate disease models poses fundamental challenges. In addition, in recent years, Drosophila has also been effectively used for low- to high-throughput drug screens and target discovery in the context of therapeutic tests for central nervous system disorders, inflammatory disorders, cardiovascular disease, cancer, and diabetes. According to PubMed, in 2022, almost 1,800 papers had been published reporting the keywords “Drosophila melanogaster”, showing that this model system is still enormously useful, even after more than 120 years of history.

The aim of this Special Issue is to collect the most up-to-date research showing the use of the fruit fly to study human conditions. We welcome the submission of original research and review articles in this field and all contributions which provide novel insights into how Drosophila models have contributed remarkably to our understanding of human pathologies.

Dr. Maria Grazia Giansanti
Dr. Roberto Piergentili
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • model organism
  • human disease
  • inherited disease
  • cancer
  • neurodegeneration
  • rare disease
  • genetics

Published Papers (6 papers)

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Research

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14 pages, 4520 KiB  
Article
A Novel Drosophila Model of Alzheimer’s Disease to Study Aβ Proteotoxicity in the Digestive Tract
by Greta Elovsson, Therése Klingstedt, Mikaela Brown, K. Peter R. Nilsson and Ann-Christin Brorsson
Int. J. Mol. Sci. 2024, 25(4), 2105; https://doi.org/10.3390/ijms25042105 - 09 Feb 2024
Viewed by 1038
Abstract
Amyloid-β (Aβ) proteotoxicity is associated with Alzheimer’s disease (AD) and is caused by protein aggregation, resulting in neuronal damage in the brain. In the search for novel treatments, Drosophila melanogaster has been extensively used to screen for anti-Aβ proteotoxic agents in studies where toxic [...] Read more.
Amyloid-β (Aβ) proteotoxicity is associated with Alzheimer’s disease (AD) and is caused by protein aggregation, resulting in neuronal damage in the brain. In the search for novel treatments, Drosophila melanogaster has been extensively used to screen for anti-Aβ proteotoxic agents in studies where toxic Aβ peptides are expressed in the fly brain. Since drug molecules often are administered orally there is a risk that they fail to reach the brain, due to their inability to cross the brain barrier. To circumvent this problem, we have designed a novel Drosophila model that expresses the Aβ peptides in the digestive tract. In addition, a built-in apoptotic sensor provides a fluorescent signal from the green fluorescent protein as a response to caspase activity. We found that expressing different variants of Aβ1–42 resulted in proteotoxic phenotypes such as reduced longevity, aggregate deposition, and the presence of apoptotic cells. Taken together, this gut-based Aβ-expressing fly model can be used to study the mechanisms behind Aβ proteotoxicity and to identify different substances that can modify Aβ proteotoxicity. Full article
(This article belongs to the Special Issue Drosophila: A Versatile Model in Biology and Medicine)
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13 pages, 4200 KiB  
Article
A Drosophila Model Reveals the Potential Role for mtt in Retinal Disease
by Wenfeng Chen, Wenmiao Zhong, Lingqi Yu, Xiang Lin, Jiayu Xie and Zhenxing Liu
Int. J. Mol. Sci. 2024, 25(2), 899; https://doi.org/10.3390/ijms25020899 - 11 Jan 2024
Viewed by 623
Abstract
Congenital stationary night blindness (CSNB) is a genetically heterogeneous inherited retinal disorder, caused by over 300 mutations in 17 different genes. While there are numerous fly models available for simulating ocular diseases, most are focused on mimicking retinitis pigmentosa (RP), with animal models [...] Read more.
Congenital stationary night blindness (CSNB) is a genetically heterogeneous inherited retinal disorder, caused by over 300 mutations in 17 different genes. While there are numerous fly models available for simulating ocular diseases, most are focused on mimicking retinitis pigmentosa (RP), with animal models specifically addressing CSNB limited to mammals. Here, we present a CSNB fly model associated with the mtt gene, utilizing RNA interference (RNAi) to silence the mtt gene in fly eyes (homologous to the mammalian GRM6 gene) and construct a CSNB model. Through this approach, we observed significant defects in the eye structure and function upon reducing mtt expression in fly eyes. This manifested as disruptions in the compound eye lens structure and reduced sensitivity to light responses. These results suggest a critical role for mtt in the function of fly adult eyes. Interestingly, we found that the mtt gene is not expressed in the photoreceptor neurons of adult flies but is localized to the inner lamina neurons. In summary, these results underscore the crucial involvement of mtt in fly retinal function, providing a framework for understanding the pathogenic mechanisms of CSNB and facilitating research into potential therapeutic interventions. Full article
(This article belongs to the Special Issue Drosophila: A Versatile Model in Biology and Medicine)
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9 pages, 2284 KiB  
Communication
Tyrosine Metabolism Pathway Is Downregulated in Dopaminergic Neurons with LRRK2 Overexpression in Drosophila
by Jack Cheng, Bor-Tsang Wu, Hsin-Ping Liu and Wei-Yong Lin
Int. J. Mol. Sci. 2023, 24(21), 15587; https://doi.org/10.3390/ijms242115587 - 25 Oct 2023
Viewed by 1066
Abstract
LRRK2 mutations are the leading cause of familial Parkinson’s disease (PD) and are a significant risk factor for idiopathic PD cases. However, the molecular mechanisms underlying the degeneration of dopaminergic (DA) neurons in LRRK2 PD patients remain unclear. To determine the translatomic impact [...] Read more.
LRRK2 mutations are the leading cause of familial Parkinson’s disease (PD) and are a significant risk factor for idiopathic PD cases. However, the molecular mechanisms underlying the degeneration of dopaminergic (DA) neurons in LRRK2 PD patients remain unclear. To determine the translatomic impact of LRRK2 expression in DA neurons, we employed gene set enrichment analysis (GSEA) to analyze a translating ribosome affinity purification (TRAP) RNA-seq dataset from a DA-neuron-specific-expressing Drosophila model. We found that the tyrosine metabolism pathway, including tyrosine hydroxylase (TH), is downregulated in DA neurons with LRRK2 overexpression; in contrast, the Hippo signaling pathway is downregulated in the G2019S mutant compared to wild-type LRRK2 in the DA neurons. These results imply that the downregulation of tyrosine metabolism occurs before pronounced DA neuron loss and that LRRK2 may downregulate the tyrosine metabolism in a DA-neuron-loss-independent way. Full article
(This article belongs to the Special Issue Drosophila: A Versatile Model in Biology and Medicine)
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Review

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17 pages, 1472 KiB  
Review
A Closer Look at Histamine in Drosophila
by Cinzia Volonté, Francesco Liguori and Susanna Amadio
Int. J. Mol. Sci. 2024, 25(8), 4449; https://doi.org/10.3390/ijms25084449 - 18 Apr 2024
Viewed by 287
Abstract
The present work intends to provide a closer look at histamine in Drosophila. This choice is motivated firstly because Drosophila has proven over the years to be a very simple, but powerful, model organism abundantly assisting scientists in explaining not only normal [...] Read more.
The present work intends to provide a closer look at histamine in Drosophila. This choice is motivated firstly because Drosophila has proven over the years to be a very simple, but powerful, model organism abundantly assisting scientists in explaining not only normal functions, but also derangements that occur in higher organisms, not excluding humans. Secondly, because histamine has been demonstrated to be a pleiotropic master molecule in pharmacology and immunology, with increasingly recognized roles also in the nervous system. Indeed, it interacts with various neurotransmitters and controls functions such as learning, memory, circadian rhythm, satiety, energy balance, nociception, and motor circuits, not excluding several pathological conditions. In view of this, our review is focused on the knowledge that the use of Drosophila has added to the already vast histaminergic field. In particular, we have described histamine’s actions on photoreceptors sustaining the visual system and synchronizing circadian rhythms, but also on temperature preference, courtship behavior, and mechanosensory transmission. In addition, we have highlighted the pathophysiological consequences of mutations on genes involved in histamine metabolism and signaling. By promoting critical discussion and further research, our aim is to emphasize and renew the importance of histaminergic research in biomedicine through the exploitation of Drosophila, hopefully extending the scientific debate to the academic, industry, and general public audiences. Full article
(This article belongs to the Special Issue Drosophila: A Versatile Model in Biology and Medicine)
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25 pages, 7622 KiB  
Review
Mitochondrial Differentiation during Spermatogenesis: Lessons from Drosophila melanogaster
by Viktor Vedelek, Ferenc Jankovics, János Zádori and Rita Sinka
Int. J. Mol. Sci. 2024, 25(7), 3980; https://doi.org/10.3390/ijms25073980 - 03 Apr 2024
Viewed by 595
Abstract
Numerous diseases can arise as a consequence of mitochondrial malfunction. Hence, there is a significant focus on studying the role of mitochondria in cancer, ageing, neurodegenerative diseases, and the field of developmental biology. Mitochondria could exist as discrete organelles in the cell; however, [...] Read more.
Numerous diseases can arise as a consequence of mitochondrial malfunction. Hence, there is a significant focus on studying the role of mitochondria in cancer, ageing, neurodegenerative diseases, and the field of developmental biology. Mitochondria could exist as discrete organelles in the cell; however, they have the ability to fuse, resulting in the formation of interconnected reticular structures. The dynamic changes between these forms correlate with mitochondrial function and mitochondrial health, and consequently, there is a significant scientific interest in uncovering the specific molecular constituents that govern these transitions. Moreover, the specialized mitochondria display a wide array of variable morphologies in their cristae formations. These inner mitochondrial structures are closely associated with the specific functions performed by the mitochondria. In multiple cases, the presence of mitochondrial dysfunction has been linked to male sterility, as it has been observed to cause a range of abnormal spermatogenesis and sperm phenotypes in different species. This review aims to elucidate the dynamic alterations and functions of mitochondria in germ cell development during the spermatogenesis of Drosophila melanogaster. Full article
(This article belongs to the Special Issue Drosophila: A Versatile Model in Biology and Medicine)
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21 pages, 2634 KiB  
Review
Multiple Roles of dXNP and dADD1—Drosophila Orthologs of ATRX Chromatin Remodeler
by Larisa Melnikova and Anton Golovnin
Int. J. Mol. Sci. 2023, 24(22), 16486; https://doi.org/10.3390/ijms242216486 - 18 Nov 2023
Viewed by 1012
Abstract
The Drosophila melanogaster dADD1 and dXNP proteins are orthologues of the ADD and SNF2 domains of the vertebrate ATRX (Alpha-Thalassemia with mental Retardation X-related) protein. ATRX plays a role in general molecular processes, such as regulating chromatin status and gene expression, while dADD1 [...] Read more.
The Drosophila melanogaster dADD1 and dXNP proteins are orthologues of the ADD and SNF2 domains of the vertebrate ATRX (Alpha-Thalassemia with mental Retardation X-related) protein. ATRX plays a role in general molecular processes, such as regulating chromatin status and gene expression, while dADD1 and dXNP have similar functions in the Drosophila genome. Both ATRX and dADD1/dXNP interact with various protein partners and participate in various regulatory complexes. Disruption of ATRX expression in humans leads to the development of α-thalassemia and cancer, especially glioma. However, the mechanisms that allow ATRX to regulate various cellular processes are poorly understood. Studying the functioning of dADD1/dXNP in the Drosophila model may contribute to understanding the mechanisms underlying the multifunctional action of ATRX and its connection with various cellular processes. This review provides a brief overview of the currently available information in mammals and Drosophila regarding the roles of ATRX, dXNP, and dADD1. It discusses possible mechanisms of action of complexes involving these proteins. Full article
(This article belongs to the Special Issue Drosophila: A Versatile Model in Biology and Medicine)
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