The trithorax Group Genemoira Encodes a Brahma-Associated Putative Chromatin-Remodeling Factor in Drosophila melanogaster

ABSTRACT The genes of the trithorax group (trxG) inDrosophila melanogaster are required to maintain the pattern of homeotic gene expression that is established early in embryogenesis by the transient expression of the segmentation genes. The precise role of each of the diverse trxG members and the functional relationships among them are not well understood. Here, we report on the isolation of the trxG gene moira(mor) and its molecular characterization. morencodes a fruit fly homolog of the human and yeast chromatin-remodeling factors BAF170, BAF155, and SWI3. mor is widely expressed throughout development, and its 170-kDa protein product is present in many embryonic tissues. In vitro, MOR can bind to itself and it interacts with Brahma (BRM), an SWI2-SNF2 homolog, with which it is associated in embryonic nuclear extracts. The leucine zipper motif of MOR is likely to participate in self-oligomerization; the equally conserved SANT domain, for which no function is known, may be required for optimal binding to BRM. MOR thus joins BRM and Snf5-related 1 (SNR1), two known Drosophila SWI-SNF subunits that act as positive regulators of the homeotic genes. These observations provide a molecular explanation for the phenotypic and genetic relationships among several of the trxG genes by suggesting that they encode evolutionarily conserved components of a chromatin-remodeling complex.

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The Drosophila Brahma complex is an essential coactivator for the trithorax group protein Zeste

Genes & Development ◽

10.1101/gad.14.9.1058 ◽

2000 ◽

Vol 14 (9) ◽

pp. 1058-1071 ◽

Cited By ~ 5

Author(s):

Arnoud J. Kal ◽

Tokameh Mahmoudi ◽

Naomi B. Zak ◽

C. Peter Verrijzer

Keyword(s):

Chromatin Remodeling ◽

Transcriptional Activation ◽

Leucine Zipper ◽

Homeotic Genes ◽

Trithorax Group ◽

Trxg Protein ◽

Chromatin Remodeling Complex ◽

Direct Binding ◽

Group Protein ◽

Brahma Complex

The trithorax group (trxG) of activators andPolycomb group (PcG) of repressors are believed to control the expression of several key developmental regulators by changing the structure of chromatin. Here, we have sought to dissect the requirements for transcriptional activation by the DrosophilatrxG protein Zeste, a DNA-binding activator of homeotic genes. Reconstituted transcription reactions established that the Brahma (BRM) chromatin-remodeling complex is essential for Zeste-directed activation on nucleosomal templates. Because it is not required for Zeste to bind to chromatin, the BRM complex appears to act after promoter binding by the activator. Purification of the Drosophila BRM complex revealed a number of novel subunits. We found that Zeste tethers the BRM complex via direct binding to specific subunits, including trxG proteins Moira (MOR) and OSA. The leucine zipper of Zeste mediates binding to MOR. Interestingly, although the Imitation Switch (ISWI) remodelers are potent nucleosome spacing factors, they are dispensable for transcriptional activation by Zeste. Thus, there is a distinction between general chromatin restructuring and transcriptional coactivation by remodelers. These results establish that different chromatin remodeling factors display distinct functional properties and provide novel insights into the mechanism of their targeting.

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Fly-on-a-Chip: Microfluidics for Drosophila melanogaster Studies

Integrative Biology ◽

10.1093/intbio/zyz037 ◽

2019 ◽

Vol 11 (12) ◽

pp. 425-443 ◽

Cited By ~ 2

Author(s):

Alireza Zabihihesari ◽

Arthur J Hilliker ◽

Pouya Rezai

Keyword(s):

Drosophila Melanogaster ◽

Developmental Stages ◽

Model Organism ◽

Fruit Fly ◽

In Vitro Assays ◽

Behavioral Studies ◽

And Behavior ◽

Manual Manipulation

Abstract The fruit fly or Drosophila melanogaster has been used as a promising model organism in genetics, developmental and behavioral studies as well as in the fields of neuroscience, pharmacology, and toxicology. Not only all the developmental stages of Drosophila, including embryonic, larval, and adulthood stages, have been used in experimental in vivo biology, but also the organs, tissues, and cells extracted from this model have found applications in in vitro assays. However, the manual manipulation, cellular investigation and behavioral phenotyping techniques utilized in conventional Drosophila-based in vivo and in vitro assays are mostly time-consuming, labor-intensive, and low in throughput. Moreover, stimulation of the organism with external biological, chemical, or physical signals requires precision in signal delivery, while quantification of neural and behavioral phenotypes necessitates optical and physical accessibility to Drosophila. Recently, microfluidic and lab-on-a-chip devices have emerged as powerful tools to overcome these challenges. This review paper demonstrates the role of microfluidic technology in Drosophila studies with a focus on both in vivo and in vitro investigations. The reviewed microfluidic devices are categorized based on their applications to various stages of Drosophila development. We have emphasized technologies that were utilized for tissue- and behavior-based investigations. Furthermore, the challenges and future directions in Drosophila-on-a-chip research, and its integration with other advanced technologies, will be discussed.

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The Drosophila kismet gene is related to chromatin-remodeling factors and is required for both segmentation and segment identity

Development ◽

10.1242/dev.126.6.1175 ◽

1999 ◽

Vol 126 (6) ◽

pp. 1175-1187 ◽

Cited By ~ 15

Author(s):

G. Daubresse ◽

R. Deuring ◽

L. Moore ◽

O. Papoulas ◽

I. Zakrajsek ◽

...

Keyword(s):

Chromatin Remodeling ◽

Homeotic Genes ◽

Loss Of Function ◽

Larval Body ◽

Sex Combs Reduced ◽

Trithorax Group ◽

Sex Combs ◽

Pair Rule Gene ◽

Body Segmentation ◽

Group Protein

The Drosophila kismet gene was identified in a screen for dominant suppressors of Polycomb, a repressor of homeotic genes. Here we show that kismet mutations suppress the Polycomb mutant phenotype by blocking the ectopic transcription of homeotic genes. Loss of zygotic kismet function causes homeotic transformations similar to those associated with loss-of-function mutations in the homeotic genes Sex combs reduced and Abdominal-B. kismet is also required for proper larval body segmentation. Loss of maternal kismet function causes segmentation defects similar to those caused by mutations in the pair-rule gene even-skipped. The kismet gene encodes several large nuclear proteins that are ubiquitously expressed along the anterior-posterior axis. The Kismet proteins contain a domain conserved in the trithorax group protein Brahma and related chromatin-remodeling factors, providing further evidence that alterations in chromatin structure are required to maintain the spatially restricted patterns of homeotic gene transcription.

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The Drosophila trithorax group proteins BRM, ASH1 and ASH2 are subunits of distinct protein complexes

Development ◽

10.1242/dev.125.20.3955 ◽

1998 ◽

Vol 125 (20) ◽

pp. 3955-3966 ◽

Cited By ~ 26

Author(s):

O. Papoulas ◽

S.J. Beek ◽

S.L. Moseley ◽

C.M. McCallum ◽

M. Sarte ◽

...

Keyword(s):

Chromatin Remodeling ◽

Protein Complexes ◽

Dominant Negative ◽

Homeotic Genes ◽

Atpase Subunit ◽

Trithorax Group ◽

Chromatin Remodeling Complexes ◽

Trithorax Group Proteins ◽

Drosophila Embryos

The trithorax group gene brahma (brm) encodes an activator of Drosophila homeotic genes that functions as the ATPase subunit of a large protein complex. To determine if BRM physically interacts with other trithorax group proteins, we purified the BRM complex from Drosophila embryos and analyzed its subunit composition. The BRM complex contains at least seven major polypeptides. Surprisingly, the majority of the subunits of the BRM complex are not encoded by trithorax group genes. Furthermore, a screen for enhancers of a dominant-negative brm mutation identified only one trithorax group gene, moira (mor), that appears to be essential for brm function in vivo. Four of the subunits of the BRM complex are related to subunits of the yeast chromatin remodeling complexes SWI/SNF and RSC. The BRM complex is even more highly related to the human BRG1 and hBRM complexes, but lacks the subunit heterogeneity characteristic of these complexes. We present biochemical evidence for the existence of two additional complexes containing trithorax group proteins: a 2 MDa ASH1 complex and a 500 kDa ASH2 complex. These findings suggest that BRM plays a role in chromatin remodeling that is distinct from the function of most other trithorax group proteins.

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Syntaxin1A-mediated Resistance and Hypersensitivity to Isoflurane in Drosophila melanogaster

Anesthesiology ◽

10.1097/aln.0000000000000629 ◽

2015 ◽

Vol 122 (5) ◽

pp. 1060-1074 ◽

Cited By ~ 12

Author(s):

Oressia H. Zalucki ◽

Hareesh Menon ◽

Benjamin Kottler ◽

Richard Faville ◽

Rebecca Day ◽

...

Keyword(s):

Drosophila Melanogaster ◽

Amino Acid ◽

General Anesthesia ◽

Fruit Fly ◽

Receptor Protein ◽

General Anesthetics ◽

Synaptic Release ◽

Protein Receptor ◽

Study Results

Abstract Background: Recent evidence suggests that general anesthetics activate endogenous sleep pathways, yet this mechanism cannot explain the entirety of general anesthesia. General anesthetics could disrupt synaptic release processes, as previous work in Caenorhabditis elegans and in vitro cell preparations suggested a role for the soluble NSF attachment protein receptor protein, syntaxin1A, in mediating resistance to several general anesthetics. The authors questioned whether the syntaxin1A-mediated effects found in these reductionist systems reflected a common anesthetic mechanism distinct from sleep-related processes. Methods: Using the fruit fly model, Drosophila melanogaster, the authors investigated the relevance of syntaxin1A manipulations to general anesthesia. The authors used different behavioral and electrophysiological endpoints to test the effect of syntaxin1A mutations on sensitivity to isoflurane. Results: The authors found two syntaxin1A mutations that confer opposite general anesthesia phenotypes: syxH3-C, a 14-amino acid deletion mutant, is resistant to isoflurane (n = 40 flies), and syxKARRAA, a strain with two amino acid substitutions, is hypersensitive to the drug (n = 40 flies). Crucially, these opposing effects are maintained across different behavioral endpoints and life stages. The authors determined the isoflurane sensitivity of syxH3-C at the larval neuromuscular junction to assess effects on synaptic release. The authors find that although isoflurane slightly attenuates synaptic release in wild-type animals (n = 8), syxH3-C preserves synaptic release in the presence of isoflurane (n = 8). Conclusion: The study results are evidence that volatile general anesthetics target synaptic release mechanisms; in addition to first activating sleep pathways, a major consequence of these drugs may be to decrease the efficacy of neurotransmission.

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Transcriptional and genomic parallels between the monoxenous parasiteHerpetomonas muscarumandLeishmania

10.1101/692178 ◽

2019 ◽

Author(s):

Megan A. Sloan ◽

Karen Brooks ◽

Thomas D. Otto ◽

Mandy J. Sanders ◽

James A. Cotton ◽

...

Keyword(s):

Drosophila Melanogaster ◽

Leishmania Major ◽

Neglected Tropical Diseases ◽

Fruit Fly ◽

Sand Fly ◽

Suitable Model ◽

Insect Host ◽

Causative Agents ◽

Trypanosomatid Parasites

AbstractTrypanosomatid parasites are causative agents of important human and animal diseases such as sleeping sickness and leishmaniasis. Most trypanosomatids are transmitted to their mammalian hosts by insects, often belonging to Diptera (or true flies). These are called dixenous trypanosomatids since they infect two different hosts, in contrast to those that infect just insects (monoxenous). However, it is still unclear whether dixenous and monoxenous trypanosomatids interact similarly with their insect host, as fly-monoxenous trypanosomatid interaction systems are rarely reported and under-studied – despite being common in nature. Here we present the genome of monoxenous trypanosomatidHerpetomonas muscarumand discuss its transcriptome duringin vitroculture and during infection of its natural insect hostDrosophila melanogaster. TheH. muscarumgenome is broadly syntenic with that of human parasiteLeishmania major. We also found strong similarities between theH. muscarumtranscriptome during fruit fly infection, and those ofLeishmaniaduring sand fly infections. Overall this suggestsDrosophila-Herpetomonasis a suitable model for less accessible insect-trypanosomatid host-parasite systems such as sandfly-Leishmania.Author SummaryTrypanosomes andLeishmaniaare parasites that cause serious Neglected Tropical Diseases (NTDs) in the world’s poorest people. Both of these are dixenous trypanosomatids, transmitted to humans and other mammals by biting flies. They are called dixenous as they can establish infections in two different types of hosts – insect vectors and mammals. In contrast, monoxenous trypanosomatids usually only infect insects. Despite establishment in the insect’s midgut being key to transmission of NTDs, events during early establishment inside the insect are still unclear in both dixenous and monoxenous parasites. Here, we study the interaction between a model insect – the fruit flyDrosophila melanogaster– and its natural monoxenous trypanosomatid parasiteHerpetomonas muscarum. We show that both the genome of this parasite, and gene regulation at early stages of infection have strong parallels withLeishmania. This work has begun to identify evolutionarily conserved aspects of the process by which trypanosomatids establish in insects, thus potentially highlighting key checkpoints necessary for transmission of dixenous parasites. In turn, this might inform new strategies to control trypanosomatid NTDs.

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The Lantibiotic NAI-107 Efficiently Rescues Drosophila melanogaster from Infection with Methicillin-Resistant Staphylococcus aureus USA300

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02965-15 ◽

2016 ◽

Vol 60 (9) ◽

pp. 5427-5436 ◽

Cited By ~ 11

Author(s):

Thomas T. Thomsen ◽

Biljana Mojsoska ◽

João C. S. Cruz ◽

Stefano Donadio ◽

Håvard Jenssen ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Drosophila Melanogaster ◽

Drug Evaluation ◽

Cost Effective ◽

Fruit Fly ◽

Antibacterial Peptides ◽

Methicillin Resistant ◽

Content Type

ABSTRACTWe used the fruit flyDrosophila melanogasteras a cost-effectivein vivomodel to evaluate the efficacy of novel antibacterial peptides and peptoids for treatment of methicillin-resistantStaphylococcus aureus(MRSA) infections. A panel of peptides with known antibacterial activityin vitroand/orin vivowas tested inDrosophila. Although most peptides and peptoids that were effectivein vitrofailed to rescue lethal effects ofS. aureusinfectionsin vivo, we found that two lantibiotics, nisin and NAI-107, rescued adult flies from fatal infections. Furthermore, NAI-107 rescued mortality of infection with the MRSA strain USA300 with an efficacy equivalent to that of vancomycin, a widely applied antibiotic for the treatment of serious MRSA infections. These results establishDrosophilaas a useful model forin vivodrug evaluation of antibacterial peptides.

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Drosophila melanogaster: A Powerful Tiny Animal Model for the Study of Metabolic Hepatic Diseases

Frontiers in Physiology ◽

10.3389/fphys.2021.728407 ◽

2021 ◽

Vol 12 ◽

Author(s):

Karen C. M. Moraes ◽

Jacques Montagne

Keyword(s):

Drosophila Melanogaster ◽

Large Scale ◽

Low Cost ◽

Fruit Fly ◽

Short Review ◽

Alcoholic Fatty Liver ◽

Hepatic Diseases ◽

Molecular Aspects ◽

Innovative Approaches

Animal experimentation is limited by unethical procedures, time-consuming protocols, and high cost. Thus, the development of innovative approaches for disease treatment based on alternative models in a fast, safe, and economic manner is an important, yet challenging goal. In this paradigm, the fruit-fly Drosophila melanogaster has become a powerful model for biomedical research, considering its short life cycle and low-cost maintenance. In addition, biological processes are conserved and homologs of ∼75% of human disease-related genes are found in the fruit-fly. Therefore, this model has been used in innovative approaches to evaluate and validate the functional activities of candidate molecules identified via in vitro large-scale analyses, as putative agents to treat or reverse pathological conditions. In this context, Drosophila offers a powerful alternative to investigate the molecular aspects of liver diseases, since no effective therapies are available for those pathologies. Non-alcoholic fatty liver disease is the most common form of chronic hepatic dysfunctions, which may progress to the development of chronic hepatitis and ultimately to cirrhosis, thereby increasing the risk for hepatocellular carcinoma (HCC). This deleterious situation reinforces the use of the Drosophila model to accelerate functional research aimed at deciphering the mechanisms that sustain the disease. In this short review, we illustrate the relevance of using the fruit-fly to address aspects of liver pathologies to contribute to the biomedical area.

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Hox dosage contributes to flight appendage morphology in Drosophila

Nature Communications ◽

10.1038/s41467-021-23293-8 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Rachel Paul ◽

Guillaume Giraud ◽

Katrin Domsch ◽

Marilyne Duffraisse ◽

Frédéric Marmigère ◽

...

Keyword(s):

Drosophila Melanogaster ◽

Differential Expression ◽

Hox Genes ◽

Expression Profiles ◽

Fruit Fly ◽

Insect Species ◽

Wing Morphology ◽

Hox Proteins ◽

Spatial Expression ◽

Flying Insects

AbstractFlying insects have invaded all the aerial space on Earth and this astonishing radiation could not have been possible without a remarkable morphological diversification of their flight appendages. Here, we show that characteristic spatial expression profiles and levels of the Hox genes Antennapedia (Antp) and Ultrabithorax (Ubx) underlie the formation of two different flight organs in the fruit fly Drosophila melanogaster. We further demonstrate that flight appendage morphology is dependent on specific Hox doses. Interestingly, we find that wing morphology from evolutionary distant four-winged insect species is also associated with a differential expression of Antp and Ubx. We propose that variation in the spatial expression profile and dosage of Hox proteins is a major determinant of flight appendage diversification in Drosophila and possibly in other insect species during evolution.

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A hybrid model based on general regression neural network and fruit fly optimization algorithm for forecasting and optimizing paclitaxel biosynthesis in Corylus avellana cell culture

Plant Methods ◽

10.1186/s13007-021-00714-9 ◽

2021 ◽

Vol 17 (1) ◽

Author(s):

Mina Salehi ◽

Siamak Farhadi ◽

Ahmad Moieni ◽

Naser Safaie ◽

Mohsen Hesami

Keyword(s):

Neural Network ◽

Fruit Fly ◽

Corylus Avellana ◽

General Regression Neural Network ◽

Fruit Fly Optimization Algorithm ◽

Harvesting Time ◽

Fruit Fly Optimization ◽

General Regression ◽

Concentration Levels

Abstract Background Paclitaxel is a well-known chemotherapeutic agent widely applied as a therapy for various types of cancers. In vitro culture of Corylus avellana has been named as a promising and low-cost strategy for paclitaxel production. Fungal elicitors have been reported as an impressive strategy for improving paclitaxel biosynthesis in cell suspension culture (CSC) of C. avellana. The objectives of this research were to forecast and optimize growth and paclitaxel biosynthesis based on four input variables including cell extract (CE) and culture filtrate (CF) concentration levels, elicitor adding day and CSC harvesting time in C. avellana cell culture, as a case study, using general regression neural network-fruit fly optimization algorithm (GRNN-FOA) via data mining approach for the first time. Results GRNN-FOA models (0.88–0.97) showed the superior prediction performances as compared to regression models (0.57–0.86). Comparative analysis of multilayer perceptron-genetic algorithm (MLP-GA) and GRNN-FOA showed very slight difference between two models for dry weight (DW), intracellular and extracellular paclitaxel in testing subset, the unseen data. However, MLP-GA was slightly more accurate as compared to GRNN-FOA for total paclitaxel and extracellular paclitaxel portion in testing subset. The slight difference was observed in maximum growth and paclitaxel biosynthesis optimized by FOA and GA. The optimization analysis using FOA on developed GRNN-FOA models showed that optimal CE [4.29% (v/v)] and CF [5.38% (v/v)] concentration levels, elicitor adding day (17) and harvesting time (88 h and 19 min) can lead to highest paclitaxel biosynthesis (372.89 µg l−1). Conclusions Great accordance between the predicted and observed values of DW, intracellular, extracellular and total yield of paclitaxel, and also extracellular paclitaxel portion support excellent performance of developed GRNN-FOA models. Overall, GRNN-FOA as new mathematical tool may pave the way for forecasting and optimizing secondary metabolite production in plant in vitro culture.

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