scholarly journals Neural and non-neural contributions to sexual dimorphism of mid-day sleep in Drosophila: A pilot study

2015 ◽  
Author(s):  
M. Khericha ◽  
J.B. Kolenchery ◽  
E. Tauber
Keyword(s):  
Sexual Dimorphism ◽  
Fat Body ◽  
Hormone Secretion ◽  
Model Organism ◽  
Fruit Fly ◽  
Mushroom Bodies ◽  
Sexually Dimorphic ◽  
Neural Tissues ◽  
Circadian Clock Output ◽  
The Brain

AbstractMany of the characteristics associated with mammalian sleep are also observed in Drosophila, making the fruit-fly a powerful model organism for studying the genetics of this important process. Among these similarities is the presence of sexual dimorphic sleep patterns, which in flies, is manifested as increased mid-day sleep (‘siesta’) in males, compared to females. Here, we have used targeted miss-expression of the gene transformer (tra) and tra2 to either feminise or masculinise specific neural and non-neural tissues in the fly. Feminization of males using three different GAL4 drivers which are expressed in the mushroom bodies induced a female-like reduced siesta, while the masculinisation of females using these drivers triggered the male-like increased siesta. We also observed a similar reversal of sex-specific sleep by miss-expressing tra in the fat body, a key tissue in energy metabolism and hormone secretion. In addition, the daily expression levels of takeout, an important circadian clock output gene, were sexually dimorphic. Taken together, our experiments suggest that sleep-sexual dimorphism in Drosophila is driven by multiple neural and non-neural circuits, within and outside the brain.

scholarly journals The use of Drosophila Melanogaster as a Model Organism to study the effect of Innate Immunity on Metabolism

2020 ◽  
Author(s):  
Abeer Mohbeddin ◽  
Nawar Haj Ahmed ◽  
Layla Kamareddine
Keyword(s):  
Drosophila Melanogaster ◽  
Fat Body ◽  
Model Organism ◽  
Fruit Fly ◽  
Janus Kinase ◽  
Signal Transducer ◽  
Metabolic Homeostasis ◽  
Stat Signaling ◽  
Stat Pathway

Apart from its traditional role in disease control, recent body of evidence has implicated a role of the immune system in regulating metabolic homeostasis. Owing to the importance of this “immune-metabolic alignment” in dictating a state of health or disease, a proper mechanistic understanding of this alignment is crucial in opening up for promising therapeutic approaches against a broad range of chronic, metabolic, and inflammatory disorders like obesity, diabetes, and inflammatory bowel syndrome. In this project, we addressed the role of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) innate immune pathway in regulating different metabolic parameters using the Drosophila melanogaster (DM) fruit fly model organism. Mutant JAK/STAT pathway flies with a systemic knockdown of either Domeless (Dome) [domeG0282], the receptor that activates JAK/STAT signaling, or the signal-transducer and activator of transcription protein at 92E (Stat92E) [stat92EEY10528], were used. The results of the study revealed that blocking JAK/STAT signaling alters the metabolic profile of mutant flies. Both domeG0282 and stat92EEY10528 mutants had an increase in body weight, lipid deprivation from their fat body (lipid storage organ in flies), irregular accumulation of lipid droplets in the gut, systemic elevation of glucose and triglyceride levels, and differential down-regulation in the relative gene expression of different peptide hormones (Tachykinin, Allatostatin C, and Diuretic hormone 31) known to regulate metabolic homeostasis in flies. Because the JAK/STAT pathway is evolutionary conserved between invertebrates and vertebrates, our potential findings in the fruit fly serves as a platform for further immune-metabolic translational studies in more complex mammalian systems including humans.

scholarly journals Sexual Dimorphism in Metabolic Responses to Western Diet in Drosophila melanogaster

Biomolecules ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 33
Author(s):  
Sofie De Groef ◽  
Tom Wilms ◽  
Séverine Balmand ◽  
Federica Calevro ◽  
Patrick Callaerts
Keyword(s):  
Drosophila Melanogaster ◽  
Sexual Dimorphism ◽  
Lipid Content ◽  
Fat Body ◽  
Fruit Fly ◽  
Fruit Flies ◽  
Standard Diet ◽  
Expression Of Genes ◽  
Obesogenic Diet ◽  
Ovarian Size

Obesity is a chronic disease affecting millions of people worldwide. The fruit fly (Drosophila melanogaster) is an interesting research model to study metabolic and transcriptomic responses to obesogenic diets. However, the sex-specific differences in these responses are still understudied and perhaps underestimated. In this study, we exposed adult male and female Dahomey fruit flies to a standard diet supplemented with sugar, fat, or a combination of both. The exposure to a diet supplemented with 10% sugar and 10% fat efficiently induced an increase in the lipid content in flies, a hallmark for obesity. This increase in the lipid content was more prominent in males, while females displayed significant changes in the glycogen content. The strong effects of the diets on the ovarian size and number of mature oocytes were also present in females exposed to diets supplemented with fat and a combination of fat and sugar. In both males and females, the fat body morphology changed and was associated with an increase in the lipid content of fat cells in response to the diets. The expression of metabolism-related genes also displayed a strong sexually dimorphic response under normal conditions and in response to the sugar and/or fat-supplemented diets. Here, we showed that the exposure of adult fruit flies to an obesogenic diet containing both sugar and fat allowed studying sexual dimorphism in metabolism and the expression of genes regulating metabolism.

scholarly journals Genetics in the Honey Bee: Achievements and Prospects toward the Functional Analysis of Molecular and Neural Mechanisms Underlying Social Behaviors

Insects ◽  
2019 ◽  
Vol 10 (10) ◽  
pp. 348 ◽  
Author(s):  
Hiroki Kohno ◽  
Takeo Kubo
Keyword(s):  
Candidate Genes ◽  
Honey Bee ◽  
Genetic Manipulation ◽  
Expression Profiles ◽  
Model Organism ◽  
Social Behaviors ◽  
Forward Genetics ◽  
Mushroom Bodies ◽  
Functional Analyses ◽  
The Brain

The European honey bee is a model organism for studying social behaviors. Comprehensive analyses focusing on the differential expression profiles of genes between the brains of nurse bees and foragers, or in the mushroom bodies—the brain structure related to learning and memory, and multimodal sensory integration—has identified candidate genes related to honey bee behaviors. Despite accumulating knowledge on the expression profiles of genes related to honey bee behaviors, it remains unclear whether these genes actually regulate social behaviors in the honey bee, in part because of the scarcity of genetic manipulation methods available for application to the honey bee. In this review, we describe the genetic methods applied to studies of the honey bee, ranging from classical forward genetics to recently developed gene modification methods using transposon and CRISPR/Cas9. We then discuss future functional analyses using these genetic methods targeting genes identified by the preceding research. Because no particular genes or neurons unique to social insects have been found yet, further exploration of candidate genes/neurons correlated with sociality through comprehensive analyses of mushroom bodies in the aculeate species can provide intriguing targets for functional analyses, as well as insight into the molecular and neural bases underlying social behaviors.

scholarly journals The neuropeptide allatostatin C from clock-associated DN1p neurons generates the circadian rhythm for oogenesis

2021 ◽  
Vol 118 (4) ◽  
pp. e2016878118
Author(s):  
Chen Zhang ◽  
Ivana Daubnerova ◽  
Yong-Hoon Jang ◽  
Shu Kondo ◽  
Dušan Žitňan ◽  
...  
Keyword(s):  
Clock Genes ◽  
Biological Clock ◽  
Model Organism ◽  
Fruit Fly ◽  
Neural Substrates ◽  
Pacemaker Neurons ◽  
Insulin Producing Cells ◽  
Gonadotrophin Secretion ◽  
Show Evidence ◽  
The Brain

The link between the biological clock and reproduction is evident in most metazoans. The fruit fly Drosophila melanogaster, a key model organism in the field of chronobiology because of its well-defined networks of molecular clock genes and pacemaker neurons in the brain, shows a pronounced diurnal rhythmicity in oogenesis. Still, it is unclear how the circadian clock generates this reproductive rhythm. A subset of the group of neurons designated “posterior dorsal neuron 1” (DN1p), which are among the ∼150 pacemaker neurons in the fly brain, produces the neuropeptide allatostatin C (AstC-DN1p). Here, we report that six pairs of AstC-DN1p send inhibitory inputs to the brain insulin-producing cells, which express two AstC receptors, star1 and AICR2. Consistent with the roles of insulin/insulin-like signaling in oogenesis, activation of AstC-DN1p suppresses oogenesis through the insulin-producing cells. We show evidence that AstC-DN1p activity plays a role in generating an oogenesis rhythm by regulating juvenile hormone and vitellogenesis indirectly via insulin/insulin-like signaling. AstC is orthologous to the vertebrate neuropeptide somatostatin (SST). Like AstC, SST inhibits gonadotrophin secretion indirectly through gonadotropin-releasing hormone neurons in the hypothalamus. The functional and structural conservation linking the AstC and SST systems suggest an ancient origin for the neural substrates that generate reproductive rhythms.

scholarly journals The Fruit Fly Brain Observatory: From Structure to Function

2019 ◽  
Author(s):  
Nikul H. Ukani ◽  
Chung-Heng Yeh ◽  
Adam Tomkins ◽  
Yiyin Zhou ◽  
Dorian Florescu ◽  
...  
Keyword(s):  
Computational Models ◽  
Brain Research ◽  
Model Organism ◽  
Fruit Fly ◽  
Data Repositories ◽  
Brain Circuits ◽  
Multiple Data ◽  
Computer Scientists ◽  
Brain Data ◽  
The Brain

AbstractThe fruit fly is a key model organism for studying the activity of interconnected brain circuits. A large scattered global research community of neurobiologists and neurogeneticists, computational and theoretical neuroscientists, and computer scientists and engineers has been developing a vast trove of experimental and modeling data that has yet to be distilled into new knowledge and understanding of the functional logic of the brain. Developing open shared models, modelling tools and data repositories that can be accessed from anywhere in the world is the necessary engine for accelerating our understanding of how the brain works.To that end we developed the Fruit Fly Brain Observatory (FFBO), the next generation open-source platform to support open, collaborative Drosophila neuroscience research. FFBO provides a (i) hub for storing and integrating fruit fly brain research data from multiple data sources worldwide, (ii) unified repository of tools and methods to build, emulate and compare fruit fly brain models in health and disease, and (iii) an open framework for fruit fly brain data processing and model execution. FFBO provides access to application tools for visualizing, configuring, simulating and analyzing computational models of brain circuits of the (i) cell type map, (ii) connectome, (iii) synaptome, and (iv) activity map using intuitive queries in plain English. Tools are provided to extract the function inherent in these structural maps. All applications can be accessed with any modern browser.

scholarly journals Decoding Sex Differences in the Brain, One Worm at a Time

2018 ◽  
Vol 2 (3) ◽  
pp. 76-80 ◽  
Author(s):  
Chen Wang
Keyword(s):  
Sex Differences ◽  
Transcription Factors ◽  
Model Organism ◽  
Basic Research ◽  
Cellular Level ◽  
Sexually Dimorphic ◽  
Sexual Dimorphisms ◽  
C Elegans ◽  
Genetic Technologies ◽  
The Brain

Sex differences in the brain are prominent features across the animal kingdom. Understanding the anatomical and regulatory mechanisms behind these differences is critical for both explaining sexually dimorphic behaviors and developing sex-targeted treatments for neurological disorders. Clinical studies considering sex biases and basic research on animal models have provided much evidence for the existence of sex differences in the brain and, in a larger sense, sexual dimorphisms in the nervous system. However, due to the complexity of structure and dimorphic behaviors, it is yet unclear precisely how neuronal sexual dimorphisms are regulated on a molecular or cellular level. This commentary reviews available tools for investigating sexual dimorphisms using a simple model organism, the roundworm Caenorhabditis elegans ( C. elegans), which enables one to study gene regulation at single-cell resolution with a number of cutting-edge molecular and genetic technologies. I highlight the doublesex/mab-3 family of transcription factors, first discovered in invertebrates, and their roles in a potentially universal regulatory mechanism underlying neuronal sexual dimorphisms. Studies of these transcription factors using C. elegans, fruit flies, and vertebrates will promote our understanding of fundamental mechanisms behind sex differences in the brain.

scholarly journals Quantitative investigation reveals distinct phases in Drosophila sleep

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Xiaochan Xu ◽  
Wei Yang ◽  
Binghui Tian ◽  
Xiuwen Sui ◽  
Weilai Chi ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
General Pattern ◽  
Model Organism ◽  
Infrared Camera ◽  
Fruit Fly ◽  
Genetic Dissection ◽  
Power Law Distribution ◽  
Quantitative Investigation ◽  
Waking Up ◽  
Set Up

AbstractThe fruit fly, Drosophila melanogaster, has been used as a model organism for the molecular and genetic dissection of sleeping behaviors. However, most previous studies were based on qualitative or semi-quantitative characterizations. Here we quantified sleep in flies. We set up an assay to continuously track the activity of flies using infrared camera, which monitored the movement of tens of flies simultaneously with high spatial and temporal resolution. We obtained accurate statistics regarding the rest and sleep patterns of single flies. Analysis of our data has revealed a general pattern of rest and sleep: the rest statistics obeyed a power law distribution and the sleep statistics obeyed an exponential distribution. Thus, a resting fly would start to move again with a probability that decreased with the time it has rested, whereas a sleeping fly would wake up with a probability independent of how long it had slept. Resting transits to sleeping at time scales of minutes. Our method allows quantitative investigations of resting and sleeping behaviors and our results provide insights for mechanisms of falling into and waking up from sleep.

scholarly journals Opposing Roles of Peroxisome Proliferator-activated Receptor α and Growth Hormone in the Regulation of CYP4A11 Expression in a Transgenic Mouse Model

2009 ◽  
Vol 284 (24) ◽  
pp. 16541-16552 ◽  
Author(s):  
Üzen Savas ◽  
Daniel E. W. Machemer ◽  
Mei-Hui Hsu ◽  
Pryce Gaynor ◽  
Jerome M. Lasker ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Hormone ◽  
Transgenic Mice ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Peroxisome Proliferator ◽  
Sexually Dimorphic ◽  
Peroxisome Proliferator Activated Receptor ◽  
Liver And Kidney

CYP4A11 transgenic mice (CYP4A11 Tg) were generated to examine in vivo regulation of the human CYP4A11 gene. Expression of CYP4A11 in mice yields liver and kidney P450 4A11 levels similar to those found in the corresponding human tissues and leads to an increased microsomal capacity for ω-hydroxylation of lauric acid. Fasted CYP4A11 Tg mice exhibit 2–3-fold increases in hepatic CYP4A11 mRNA and protein, and this response is absent in peroxisome proliferator-activated receptor α (PPARα) null mice. Dietary administration of either of the PPARα agonists, fenofibrate or clofibric acid, increases hepatic and renal CYP4A11 levels by 2–3-fold, and these responses were also abrogated in PPARα null mice. Basal liver CYP4A11 levels are reduced differentially in PPARα−/− females (>95%) and males (<50%) compared with PPARα−/+ mice. Quantitative and temporal differences in growth hormone secretion are known to alter hepatic lipid metabolism and to underlie sexually dimorphic gene expression, respectively. Continuous infusion of low levels of growth hormone reduced CYP4A11 expression by 50% in PPARα-proficient male and female transgenic mice. A larger decrease was observed for the expression of CYP4A11 in PPARα−/− CYP4A11 Tg male mice to levels similar to that of female PPARα-deficient mice. These results suggest that PPARα contributes to the maintenance of basal CYP4A11 expression and mediates CYP4A11 induction in response to fibrates or fasting. In contrast, increased exposure to growth hormone down-regulates CYP4A11 expression in liver.

scholarly journals X chromosome escapee genes are involved in ischemic sexual dimorphism through epigenetic modification of inflammatory signals

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Shaohua Qi ◽  
Abdullah Al Mamun ◽  
Conelius Ngwa ◽  
Sharmeen Romana ◽  
Rodney Ritzel ◽  
...  
Keyword(s):  
Sexual Dimorphism ◽  
X Chromosome ◽  
Epigenetic Modification ◽  
Artery Occlusion ◽  
Sexually Dimorphic ◽  
Mrna Levels ◽  
Young Females ◽  
Human Stroke ◽  
Histone H3k4 ◽  
Cerebral Artery Occlusion

Abstract Background Stroke is a sexually dimorphic disease. Previous studies have found that young females are protected against ischemia compared to males, partially due to the protective effect of ovarian hormones, particularly estrogen (E2). However, there are also genetic and epigenetic effects of X chromosome dosage that contribute to stroke sensitivity and neuroinflammation after injury, especially in the aged. Genes that escape from X chromosome inactivation (XCI) contribute to sex-specific phenotypes in many disorders. Kdm5c and kdm6a are X escapee genes that demethylate H3K4me3 and H3K27me3, respectively. We hypothesized that the two demethylases play critical roles in mediating the stroke sensitivity. Methods To identify the X escapee genes involved in stroke, we performed RNA-seq in flow-sorted microglia from aged male and female wild type (WT) mice subjected to middle cerebral artery occlusion (MCAO). The expression of these genes (kdm5c/kdm6a) were confirmed in four core genotypes (FCG) mice and in post-mortem human stroke brains by immunohistochemistry (IHC), Western blot, and RT-PCR. Chromatin immunoprecipitation (ChIP) assays were conducted to detect DNA levels of inflammatory interferon regulatory factor (IRF) 4/5 precipitated by histone H3K4 and H3K27 antibodies. Manipulation of kdm5c/kdm6a expression with siRNA or lentivirus was performed in microglial culture, to determine downstream pathways and examine the regulatory roles in inflammatory cytokine production. Results Kdm5c and kdm6a mRNA levels were significantly higher in aged WT female vs. male microglia, and the sex difference also existed in ischemic brains from FCG mice and human stroke patients. The ChIP assay showed the IRF 4/5 had higher binding levels to demethylated H3K4 or H3K27, respectively, in female vs. male ischemic microglia. Knockdown or over expression of kdm5c/kdm6a with siRNA or lentivirus altered the methylation of H3K4 or H3K27 at the IRF4/5 genes, which in turn, impacted the production of inflammatory cytokines. Conclusions The KDM-Histone-IRF pathways are suggested to mediate sex differences in cerebral ischemia. Epigenetic modification of stroke-related genes constitutes an important mechanism underlying the ischemic sexual dimorphism.

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