📰 "Mapping gene expression dynamics to developmental phenotypes with information entropy analysis"
https://arxiv.org/abs/2510.04101 #DrosophilaMelanogaster #Physics.Bio-Ph
#Drosophila #Q-Bio.Qm
#Embryo
Mapping gene expression dynamics to developmental phenotypes with information entropy analysis
The development of multicellular organisms entails a deep connection between time-dependent biochemical processes taking place at the subcellular level, and the resulting macroscopic phenotypes that arise in populations of up to trillions of cells. A statistical mechanics of developmental processes would help to understand how microscopic genotypes map onto macroscopic phenotypes, a general goal across biology. Here we follow this approach, hypothesizing that development should be understood as a thermodynamic transition between non-equilibrium states. We test this hypothesis in the context of the fruit fly, Drosophila melanogaster, a model organism used widely in genetics and developmental biology for over a century. Applying a variety of information-theoretic measures to public transcriptomics datasets of whole fly embryos during development, we show that the global temporal dynamics of gene expression can be understood as a process that probabilistically guides embryonic dynamics across macroscopic phenotypic stages. In particular, we demonstrate signatures of irreversibility in the information complexity of transcriptomic dynamics, as measured mainly by the permutation entropy of indexed ensembles (PI entropy). Our results show that the dynamics of PI entropy correlate strongly with developmental stages. Overall, this is a test case in applying information complexity analysis to relate the statistical mechanics of biomarkers to macroscopic developmental dynamics.
📰 "Drosophila as an Animal Model To Determine the Functional and Behavioral Significance of Dopamine Transporter Genetic Variations Associated with Brain Disorders"
https://doi.org/doi:10.1007/978-3-031-96364-3_9https://pubmed.ncbi.nlm.nih.gov/41051712/ #DrosophilaMelanogaster #Neuroscience #DrosophilaUltrasmall Gold Nanoparticles Boost Radiotherapy and Protect against Radiation Damage
This study investigates the effects of ultrasmall (∼4 nm) gold nanoparticles (AuNPs) combined with X-ray irradiation to enhance radiotherapy efficacy. Using the in vivo Drosophila melanogaster model, we observed that while AuNPs alone delayed embryonic development, their combination with irradiation completely halted it. Lifespan analysis showed that irradiated flies fed with AuNPs had a slight survival advantage, suggesting a protective effect against radiation-induced oxidative stress. Immunofluorescence analysis revealed increased DNA damage (or repair) in the flies, supporting the potential of AuNPs to boost the local radiation dose and offer protection against radiation-induced damage, with implications for optimized therapeutic strategies.
A GPCR signaling pathway in insect odor detection
Odor detection differs fundamentally in vertebrates, which use G protein-coupled receptors (GPCRs), and insects, which employ ion channels. Here, we report the first evidence for a GPCR defining tuning properties of insect olfactory sensory neurons. Single-cell transcriptomics of the Drosophila melanogaster antenna identified selective expression of the Gγ30A subunit in acid-sensing Ir64a-DC4 neurons. Gγ30A is essential for broadening responses to long-chain acids, acting with Gαs, Gβ13F, adenylate cyclase Ac13E and the Cngl channel. We further discovered that Cirl, a latrophilin-family GPCR, is broadly-transcribed in the antenna but the protein is localized only in Ir64a-DC4 sensory cilia, dependent upon Gγ30A, but not Ir64a. Importantly, loss of Cirl also narrows Ir64a-DC4 tuning properties. Homologous neurons in Drosophila sechellia naturally exhibit narrow acid tuning, despite functional conservation of Ir64a; these differences correlate instead with lower expression of metabotropic components. Our findings reveal unexpected roles for GPCR/metabotropic signaling in olfactory detection and divergence in insects.
### Competing Interest Statement
The authors have declared no competing interest.
European Molecular Biology Organization Long-Term Fellowship, ALTF 454-2019
Marie Skłodowska-Curie Actions Individual Fellowship, 836783
Japanese Society for the Promotion of Science Overseas Research Fellowship, 202360258
National Research Foundation of Korea, RS-2023-00211007
ERC Advanced Grant, 833548
Swiss National Science Foundation, 310030_219185
UGT35B1 is the principal enzyme mediating nicotine glycosylation in Drosophila melanogaster
Nicotine is a plant-derived pyridine alkaloid with potent neurotoxic properties. A major pathway for detoxification of nicotine in mammals is via glucuronidation to produce nicotine N-glucuronide, but this process in insects remains poorly understood. Using mass spectrometry, we demonstrate that Drosophila melanogaster detoxifies nicotine through glycosylation, producing nicotine N-glycoside. Given that many new agrochemicals contain pyridine rings, we also investigated the metabolism of flonicamid and imidacloprid. We detected glycosylation of flonicamid, but not imidacloprid. A targeted RNAi screen across 21 UDP-glycosyltransferases (Ugts) identified Ugt35B1 as important for survival of nicotine exposure. CRISPR-based knockout of Ugt35B1 increases sensitivity to nicotine and flonicamid, but not to imidacloprid, nor to a structurally distinct neonicotinoid (thiamethoxam). Mass spectrometry of knockout and control flies confirms that Ugt35B1 glycosylates nicotine, its metabolite cotinine, and flonicamid. Together these findings establish Ugt35B1 as the principal UGT mediating nicotine detoxification in D. melanogaster, revealing a previously uncharacterized insect glycosylation pathway with potential implications for herbivory, insecticide detoxification and toxicology.
### Competing Interest Statement
The authors have declared no competing interest.
USDA/NIFA, 12898432
NIH Common Fund, R01AI148529
NIH Common Fund, https://ror.org/001d55x84, RO1AI148541
U.S. National Science Foundation, IOS 2024252
📰 "Comparative population genomics reveals adaptive convergence in two Drosophila species across global environments"
https://www.biorxiv.org/content/10.1101/2025.10.02.680045v1?rss=1 #DrosophilaMelanogaster #Evolution #Drosophila #Genomics📰 "Validation of Insect Dopa Decarboxylase as a Potential Insecticide Target and Discovery of Selective Lead Compounds"
https://doi.org/doi:10.1021/acs.jafc.5c09908https://pubmed.ncbi.nlm.nih.gov/41042682/ #DrosophilaMelanogaster #DrosophilaValidation of Insect Dopa Decarboxylase as a Potential Insecticide Target and Discovery of Selective Lead Compounds
Dopa decarboxylase (DDC) is a key rate-limiting enzyme involved in cuticle tanning in insects, catalyzing the conversion of l-dopa to dopamine. Given its essential role in insect survival, DDC represents a potential target for pest control. In this study, we recombinantly expressed and characterized DDC from Drosophila melanogaster and developed a structural model for virtual screening. Quercetin (Que), the first identified inhibitor of insect DDC, was found to have an IC50 value of 9.43 μM. Notably, Que displayed much lower inhibitory activity against human DDC, with an IC50 value of 29.56 μM. Sequence-structure comparisons and molecular docking revealed several amino acid differences in the catalytic loop (L330, N326, V327, and D335) that may account for the distinct substrate specificity between insect and mammalian DDCs, as well as the differential inhibitor sensitivities. Bioassays demonstrated that Que exhibited significant insecticidal activity against the lepidopteran pest Plutella xylostella and the orthopteran pest Locusta migratoria. This study not only reinforces the potential of targeting insect DDC for insecticide development but also identifies a promising lead scaffold for further insecticide design.
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