Drosophila melanogaster: How and Why It Became a Model Organism
Abstract
1. Introduction: A Brief Historical Background
2. People Who Contributed to Making the Fruit Fly a Reference Model Organism
- Walter Jakob Gehring discovered the homeobox in 1983 [21] and was also involved in the development and application of enhancer trapping methods.
- Seymour Benzer used forward genetics to investigate the genetic basis of various behaviors such as phototaxis and learning and discovered the first circadian rhythm mutants in Drosophila [24,25,26,27]. Concerning this insect, he also studied neurodegeneration and aging and isolated the first long-life mutant called Methuselah [28].
- Leslie Birgit Vosshall studied the genetic and behavioral mechanisms involved in the olfaction and feeding behavior of fruit flies, mosquitoes, and humans [43].
- Michael Ashburner identified a cascade of genetic controls in the post-larval development triggered by ecdysone (polytene chromosome puffs) [46]; he was also a member of the consortium involved in the sequencing and annotation of the Drosophila genome and actively participated in setting up the FlyBase, Gene Ontology, and ChEBI databases [47,48].
3. Why Use Drosophila melanogaster?
4. Using Drosophila melanogaster to Study Human Conditions
4.1. Drosophila melanogaster as a Model in Cancer Research
4.1.1. Drosophila Model for Colorectal Cancer
4.1.2. Drosophila Model for Lung Cancer
4.1.3. Drosophila Model for Glioblastoma Multiforme
4.2. Drosophila melanogaster as a Model for Neurodegenerative and Neurodevelopmental Diseases
4.3. Drosophila as a Model for Other Human Pathologies
4.4. Drosophila as a Model for Human Infectious Diseases
4.5. Drosophila as a Model for Drug Identification and Testing
4.6. Limits of Drosophila melanogaster When Modeling Human Diseases
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Cancer Type | Genetic Mutations | Why Drosophila | Ref. |
---|---|---|---|
Colorectal cancer | RasG12V, p53, Pten apc | Similarly to human CRC, Drosophila CRC models display altered cell differentiation and cell growth associated with the disruption of intestinal homeostasis | [81] |
Lung cancer | RasG12V Pten |
| [86] |
Lung cancer | KIF5B-RET | Drosophila KIF5B-RET model suggests novel therapeutic strategies for targeting KIF5B-RET fusions | [87] |
Glioblastoma multiforme | Glial specific expression of activated EGFR and dp110 (repo>dEGFRλ; dp110CAAX) |
| [92] |
NDD/#MIM | Human/Drosophila Gene | The Drosophila Disease Model | Ref. |
---|---|---|---|
PACS1-NDD MIM#615009 | PACS1/dPACS | Loss of dPACS leads to defects in tubulin acetylation and severe bang sensitivity, a phenotype associated with seizures | [123] |
PACS2-NDD MIM#618067 | PACS2/dPACS | Loss of dPACS leads to defects in tubulin acetylation and severe bang sensitivity, a phenotype associated with seizures | [123] |
WDR37-NDD MIM #618652 | wdr37 | Loss of wdr37 causes bang sensitivity and a defect in grip strength | [124] |
Virus Full Name | Virus Acronym | Associated Disease | Why Drosophila | Ref. |
---|---|---|---|---|
Human immune-deficiency virus 1 | HIV1 | Acquired immune deficiency syndrome (AIDS) | it allowed us to understand the role of Toll and JNK pathways during infection | [135,136] |
Dengue virus | DENV | Dengue hemorrhagic fever (DHF) | it allowed for a better understanding of the role of RNA interference (RNAi) in infection control | [137,138] |
Severe acute respiratory syndrome coronavirus | SARS-CoV | Severe acute respiratory syndrome (SARS) | it allowed for better understanding the protein–protein interactions between viral and host proteins | [139,140] |
Sindbis virus | SINV | Sindbis fever | it allowed for better understanding the entry mechanism of the virus inside cells and the role of the ERK pathway in Drosophila and mosquito (the natural virus carrier) intestinal immunity | [141,142] |
West Nile virus | WNV | West Nile fever | it allowed for exploring the possibility to control the infection via RNAi | [143,144] |
Influenza A virus | IAV | Pandemic flu | it allowed for identifying several conserved host factors important for virus replication | [145] |
Vesicular stomatitis virus | VSV | Oncolytic virus causing a flu-like condition | it allowed for studying of the role of Toll-7 in controlling virus infection | [146] |
Epstein–Barr virus | EBV | Mononucleosis; also involved in cancer and multiple sclerosis | it allowed for the identification of human EBV-targeted tumor suppressors | [147,148] |
Human cytomegalovirus | HCMV | Birth defects | it provided a model to study how HCMV impairs embryonic development | [149] |
Simian virus 40 | SV40 | Debated role in oncogenesis | possible oncogenetic routes have been disclosed in the fly | [150] |
Vaccinia virus | VACV | Rash and fever; also used as a vaccine for smallpox | it allowed for the identification of host factors required for viral entry | [151] |
Severe acute respiratory syndrome coronavirus 2 | SARS-CoV-2 | Coronavirus disease (COVID)-19 | it allowed for the identification of key functional interactions between viral factors and host proteins and its relationship with cardiovascular and neuromuscular complications in humans | [152,153,154,155,156] |
Category | Drosophila melanogaster | Homo sapiens |
---|---|---|
Organs Involved | Fat body, midgut, Malpighian tubules (analogous to liver and kidney functions) | Liver, kidneys, intestines, lungs |
Enzyme Systems | Cytochrome P450 monooxygenases (less diverse), esterases, glutathione S-transferases | Extensive cytochrome P450 families (CYP1, CYP2, CYP3), UGTs, SULTs, esterases |
Blood–Brain Barrier | Present but structurally and functionally simpler; lacks tight junctions of vertebrate BBB | Complex structure with tight junctions, astrocytic end-feet, and selective permeability |
Absorption | Primarily through ingestion; limited oral bioavailability studies | Oral, intravenous, subcutaneous, transdermal, etc. |
Distribution | Open circulatory system; hemolymph distributes compounds | Closed circulatory system; plasma protein binding and tissue perfusion |
Metabolism | Simplified metabolic pathways; limited phase I and II reactions | Complex phase I (oxidation, reduction, hydrolysis) and phase II (conjugation) metabolism |
Excretion | Malpighian tubules and hindgut; excretion into feces | Renal (urine), biliary (feces), pulmonary, and sweat excretion routes |
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Giansanti, M.G.; Frappaolo, A.; Piergentili, R. Drosophila melanogaster: How and Why It Became a Model Organism. Int. J. Mol. Sci. 2025, 26, 7485. https://doi.org/10.3390/ijms26157485
Giansanti MG, Frappaolo A, Piergentili R. Drosophila melanogaster: How and Why It Became a Model Organism. International Journal of Molecular Sciences. 2025; 26(15):7485. https://doi.org/10.3390/ijms26157485
Chicago/Turabian StyleGiansanti, Maria Grazia, Anna Frappaolo, and Roberto Piergentili. 2025. "Drosophila melanogaster: How and Why It Became a Model Organism" International Journal of Molecular Sciences 26, no. 15: 7485. https://doi.org/10.3390/ijms26157485
APA StyleGiansanti, M. G., Frappaolo, A., & Piergentili, R. (2025). Drosophila melanogaster: How and Why It Became a Model Organism. International Journal of Molecular Sciences, 26(15), 7485. https://doi.org/10.3390/ijms26157485