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Title: Characterization of Lis-1 loss of function at the neuromuscular junction of Drosophila melangaster larvae.
Creator: Vargas, Leticia, Boerner, Jana, Godenschwege, Tanja A.
Date Issued: 2013-04-05
PURL: http://purl.flvc.org/fcla/dt/3361219
Subject Headings: Lissencephaly, Drosophila melanogaster, Mutations
Format: Document (PDF)

Title: Genetic and Neural Mechanisms Regulating the Interaction Between Sleep and Metabolism in Drosophila Melanogaster.
Creator: Yurgel, Maria E., Keene, Alex C., Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: Dysregulation of sleep and metabolism has enormous health consequences. Sleep loss is linked to increased appetite and insulin insensitivity, and epidemiological studies link chronic sleep deprivation to obesity-related disorders. Interactions between sleep and metabolism involve the integration of signalling from brain regions regulating sleep, feeding, and metabolism, as well as communication between the brain and peripheral organs. In this series of studies, using the fruit fly as a model...
Show moreDysregulation of sleep and metabolism has enormous health consequences. Sleep loss is linked to increased appetite and insulin insensitivity, and epidemiological studies link chronic sleep deprivation to obesity-related disorders. Interactions between sleep and metabolism involve the integration of signalling from brain regions regulating sleep, feeding, and metabolism, as well as communication between the brain and peripheral organs. In this series of studies, using the fruit fly as a model organism, we investigated how feeding information is processed to regulate sleep, and how peripheral tissues regulate sleep through the modulation of energy stores. In order to address these questions, we performed a large RNAi screen to identify novel genetic regulators of sleep and metabolism. We found that, the mRNA/DNA binding protein, Translin (trsn), is necessary for the acute modulation of sleep in accordance with feeding state. Flies mutant for trsn or selective knockdown of trsn in Leucokinin (Lk) neurons abolishes starvation-induced sleep suppression. In addition, genetic silencing of Lk neurons or a mutation in the Lk locus also disrupts the integration between sleep and metabolism, suggesting that Lk neurons are active during starvation. We confirmed this hypothesis by measuring baseline activity during fed and starved states. We found that LHLK neurons, which have axonal projections to sleep and metabolic centers of the brain, are more active during starvation. These findings suggest that LHLK neurons are modulated in accordance with feeding state to regulate sleep. Finally, to address how peripheral tissues regulate sleep, we performed an RNAi screen, selectively knocking down genes in the fat body. We found that knockdown of Phosphoribosylformylglycinamidine synthase (Ade2), a highly conserved gene involved the biosynthesis of purines, regulates sleep and energy stores. Flies heterozygous for two Ade2 mutations are short sleepers and this effect is partially rescued by restoring Ade2 to the fly fat body. These findings suggest Ade2 functions within the fat body to promote both sleep and energy storage, providing a functional link between these processes. Together, the experimental evidence presented here provides an initial model for how the peripheral tissues communicate to the brain to modulate sleep in accordance with metabolic state.
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Date Issued: 2018
PURL: http://purl.flvc.org/fau/fd/FA00013163
Subject Headings: Drosophila melanogaster, Sleep, Metabolism
Format: Document (PDF)

Title: GENETIC SCREENS IDENTIFY NOVEL REGULATORS OF SLEEP AND METABOLISM IN DROSOPHILA MELANOGASTER.
Creator: Murakami, Kazuma N., Keene, Alex C., Florida Atlantic University, Department of Biological Sciences, Charles E. Schmidt College of Science
Abstract/Description: Proper regulation of sleep and metabolism are critical to the survival of all organisms. In humans, dysregulation of sleep is linked to metabolic syndrome, including hypertension, hyperglycemia and hyperlipidemia. However, the mechanisms regulating interactions between sleep and metabolism are poorly understood. Although the fruit fly, Drosophila melanogaster, bears little anatomical resemblance to humans, it shares similar genetics essential in understanding normal development and disease in...
Show moreProper regulation of sleep and metabolism are critical to the survival of all organisms. In humans, dysregulation of sleep is linked to metabolic syndrome, including hypertension, hyperglycemia and hyperlipidemia. However, the mechanisms regulating interactions between sleep and metabolism are poorly understood. Although the fruit fly, Drosophila melanogaster, bears little anatomical resemblance to humans, it shares similar genetics essential in understanding normal development and disease in humans. From humans to flies, many disease-related genes and pathways are highly conserved, rendering the fruit fly ideal to understanding the interactions between sleep and metabolism. Therefore, using the fruit fly provides a framework for understanding how genes function between sleep and metabolism. During starvation, both humans and rats reduce their sleep. Similarly, previous studies have shown that fruit flies also suppress sleep to forage for food, further showing that sleep and metabolism are intricately tied to one another and that they are highly conserved across species. To further explore the interactions between sleep and metabolism, I have conducted multiple genetic screens to identify novel regulators of sleep-metabolism interactions. These experiments led to the identification of the mRNA binding protein translin (trsn) as being required for starvation-induced sleep suppression. A second screen that targeted metabolic genes from a genome-wide association study identified the ion channel accessory protein uncoordinated 79 (unc79) as a critical regulator of both sleep duration and starvation resistance. The genes function in different regions of the brain and suggest complex neural circuitry is likely to underlie regulation of sleep metabolism interactions. Taken together, a mechanistic understanding of how different genes function to regulate sleep in flies will further our understanding of how sleep and metabolism is regulated in humans.
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Date Issued: 2021
PURL: http://purl.flvc.org/fau/fd/FA00013722
Subject Headings: Drosophila melanogaster, Sleep, Genetic screening
Format: Document (PDF)

Title: Does methionine sulfoxide reductase have a role in maintaining adequate dopamine levels in drosophila melanogaster?.
Creator: Hernandez, Caesar, Binninger, David, Graduate College
Date Issued: 2013-04-12
PURL: http://purl.flvc.org/fcla/dt/3361311
Subject Headings: Drosophila melanogaster, Methionine Sulfoxide Reductases, Dopamine
Format: Document (PDF)

Title: Generation of a Dichaete Gal4 strain in Drosophila Melanogaster.
Creator: Alif, Razan, Nambu, John R, Graduate College
Date Issued: 2011-04-08
PURL: http://purl.flvc.org/fcla/dt/3164456
Subject Headings: Drosophila melanogaster --Embryology, Mammals --Embryology, Y chromosome
Format: Document (PDF)

Title: Alternative Biological Roles of Methionine Sulfoxide Reductases in Drosophila melanogaster.
Creator: Wilson, Kelsey, Binninger, David, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: The oxidation of methionine (Met) into methionine sulfoxide (met-(o)) leads to deleterious modifications to a variety of cellular constituents. These deleterious alterations can be reversed by enzymes known as methionine sulfoxide reductases (Msr). The Msr (MsrA and MsrB) family of enzymes have been studied extensively for their biological roles in reducing oxidized Met residues back into functional Met. A wide range of studies have focused on Msr both in vivo and in vitro using a variety of...
Show moreThe oxidation of methionine (Met) into methionine sulfoxide (met-(o)) leads to deleterious modifications to a variety of cellular constituents. These deleterious alterations can be reversed by enzymes known as methionine sulfoxide reductases (Msr). The Msr (MsrA and MsrB) family of enzymes have been studied extensively for their biological roles in reducing oxidized Met residues back into functional Met. A wide range of studies have focused on Msr both in vivo and in vitro using a variety of model organisms. More specifically, studies have noted numerous processes affected by the overexpression, under expression, and silencing of MsrA and MsrB. Collectively, the results of these studies have shown that Msr is involved in lifespan and the management of oxidative stress. More recent evidence is emerging that supports existing biological functions of Msr and theorizes the involvement of Msr in numerous biological pathways.
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Date Issued: 2018
PURL: http://purl.flvc.org/fau/fd/FA00005980
Subject Headings: Drosophila melanogaster, Methionine Sulfoxide Reductases, Oxidative stress
Format: Document (PDF)

Title: Characterizing electroconvulsive seizure recovery time in the invertebrate model systems Caenorhabditis elegans and Drosophila melanogaster.
Creator: Risley, Monica G., Dawson-Scully, Ken, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: Seizures are a symptom of epilepsy, characterized by spontaneous firing due to an imbalance of excitatory and inhibitory features. While mammalian seizure models receive the most attention, the simplicity and tractability of invertebrate model systems, specifically C. elegans and D. melanogaster, have many advantages in understanding the molecular and cellular mechanisms of seizure behavior. This research explores C. elegans and D. melanogaster as electroconvulsive seizure models to...
Show moreSeizures are a symptom of epilepsy, characterized by spontaneous firing due to an imbalance of excitatory and inhibitory features. While mammalian seizure models receive the most attention, the simplicity and tractability of invertebrate model systems, specifically C. elegans and D. melanogaster, have many advantages in understanding the molecular and cellular mechanisms of seizure behavior. This research explores C. elegans and D. melanogaster as electroconvulsive seizure models to investigate methods to both modulate and better understand seizure susceptibility. A common underlying feature of seizures in mammals, worms, and flies involves regulating excitation and inhibition. The C. elegans locomotor circuit is regulated via well characterized GABAergic and cholingeric motoneurons that innervate two rows of dorsal and ventral body wall muscles. In this research, we developed an electroconvulsive seizure assay which utilizes the locomotor circuit as a behavioral read out of neuronal function. When inhibition is decreased in the circuit, for example by decreasing GABAergic input, we find a general increase in the time to recovery from a seizure. After establishing the contribution of excitation and inhibition to seizure recovery, we explored a ubiquitin ligase, associated with comorbidity of an X-linked Intellectual Disorder and epilepsy in humans, and established that the worm homolog, eel-1, contributes to seizure susceptibility similarly to the human gene. Next, we investigated a cGMP-dependent protein kinase (PKG) that functions in the nervous system of both worms and flies and determined that increasing PKG activity, decreases the time to recovery from an electroconvulsive seizure. These experiments suggest a potential novel role for a major protein, PKG, in seizure susceptibility and that the C. elegans and D. melanogaster electroconvulsive seizure assays can be used to investigate possible genes involved in seizure susceptibility and future therapeutic to treat epilepsy.
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Date Issued: 2018
PURL: http://purl.flvc.org/fau/fd/FA00005954
Subject Headings: Seizures, Epilepsy, Drosophila melanogaster, Caenorhabditis elegans
Format: Document (PDF)

Title: Effects of Serotonin Modulation on Methionine Sulfoxide Reductase Deficient Drosophila melanogaster.
Creator: Hamadeh, Ali, Binninger, David, Florida Atlantic University, Department of Biological Sciences, Charles E. Schmidt College of Science
Abstract/Description: Methionine sulfoxide reductase (MSR) is an important antioxidant to help mitigate oxidative stress that contributes to age-associated neurodegenerative diseases, such as Alzheimer’s Disease and Parkinson’s Disease. In MSR deficient Drosophila melanogaster (fruit flies), larvae show a developmental delay like that seen when wild-type larvae are reared on nutrient deficit culture medium. These investigators further showed that serotonin levels were depressed in these nutrient deficient larvae....
Show moreMethionine sulfoxide reductase (MSR) is an important antioxidant to help mitigate oxidative stress that contributes to age-associated neurodegenerative diseases, such as Alzheimer’s Disease and Parkinson’s Disease. In MSR deficient Drosophila melanogaster (fruit flies), larvae show a developmental delay like that seen when wild-type larvae are reared on nutrient deficit culture medium. These investigators further showed that serotonin levels were depressed in these nutrient deficient larvae. The overarching aim of this study was to better understand the role of serotonin in MSR regulated physiology. Supplementing food with serotonin partially rescued the slower mouth hook movements (MHM) observed in the MSR-deficient flies. However, supplementation with serotonin altering drugs that cross the blood brain barrier (5-hydroxytryptophan, fluoxetine, or paravi chlorophenylalanine) did not rescue MHM and caused impairments to the growth of larvae during development. This study indicates that serotonin regulates feeding behavior partially through the regulation of MSR production but acts independently to regulate development.
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Date Issued: 2021
PURL: http://purl.flvc.org/fau/fd/FA00013761
Subject Headings: Drosophila melanogaster, Methionine sulfoxide reductase, Serotonin
Format: Document (PDF)

Title: Discovery and biological characterization of conotoxins from the venom of Conus Brunneus in Drosophila Melanogaster.
Creator: Heghinian, Mari D., Mari, Frank, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description: Cone snails are venomous marine predators whose venom is a complex mixture of modified peptides (conopeptides). Conopeptides have direct specificity towards voltage- and ligand-gated ion channels and G-protein coupled receptors. More specifically, alpha conotoxins target nicotinic acetylcholine receptors (nAChR) and are of great interest as probes for different nAChR subtypes involved in a broad range of neurological function. Typically, the amount of peptide provided directly from the cone...
Show moreCone snails are venomous marine predators whose venom is a complex mixture of modified peptides (conopeptides). Conopeptides have direct specificity towards voltage- and ligand-gated ion channels and G-protein coupled receptors. More specifically, alpha conotoxins target nicotinic acetylcholine receptors (nAChR) and are of great interest as probes for different nAChR subtypes involved in a broad range of neurological function. Typically, the amount of peptide provided directly from the cone snails (from either dissected or “milked” venom) is minimal, thus hindering the wide use of bioassay-guided approaches for compound discovery. Biochemical-based approaches for discovery by means of identification and characterization of venom components can be used due to their compatibility with the small quantities of cone snail venom available; however, no direct assessment of the bioactivity can be gleaned from these approaches. Therefore, newly discovered conotoxins must be acquired synthetically, which can be difficult due to their complicated folding motifs. The ability to test small quantities of peptide for bioactivity during the purification process can lead to the discovery of novel components using more direct approaches. Presented here is the description of use of an effective method of bioassay-guided fractionation for the discovery of novel alpha conotoxins as well as further biological characterization of other known alpha conotoxins. This method requires minimal amounts of sample and evaluates, via in vivo electrophysiological measurements, the effect of conotoxins on the functional outputs of a well-characterized neuronal circuit in Drosophila melanogaster known as the giant fiber system. Our approach uses reversed-phase HPLC fractions from venom dissected from the ducts of Conus brunneus in addition to synthetic alpha conotoxins. Fractions were individually tested for activity, re-fractionated, and re-tested to narrow down the compound responsible for activity. A novel alpha conotoxin, bru1b, was discovered via the aforementioned approach. It has been fully characterized in the giant fiber system through the use of mutant flies, as well as tested in Xenopus oocytes expressing nicotinic acetylcholine channels and against the acetylcholine binding protein. Other well-known alpha conotoxins have also been characterized in the giant fiber system.
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Date Issued: 2014
PURL: http://purl.flvc.org/fau/fd/FA00004122, http://purl.flvc.org/fau/fd/FA00004122
Subject Headings: Drosophila melanogaster, Gastropoda -- venom, Peptides -- Structure, Venom
Format: Document (PDF)

Title: Development of a novel assay for in vivo screening of neuromodulatory drugs and targeted disruption of cholinergic synaptic transmission in Drosophila melanogaster.
Creator: Mejia, Monica, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: Finding novel compounds that affect neuronal or muscular function is of great interest, as they can serve as potential pharmacological agents for a variety of neurological disorders. For instance, conopeptides have been developed into powerful drugs like the painkiller PrialtTM. Most conopeptides, however, have yet to be characterized, revealing the need for a rapid and straightforward screening method. We have designed a novel bioassay, which allows for unbiased screening of biological...
Show moreFinding novel compounds that affect neuronal or muscular function is of great interest, as they can serve as potential pharmacological agents for a variety of neurological disorders. For instance, conopeptides have been developed into powerful drugs like the painkiller PrialtTM. Most conopeptides, however, have yet to be characterized, revealing the need for a rapid and straightforward screening method. We have designed a novel bioassay, which allows for unbiased screening of biological activity of compounds in vivo against numerous molecular targets on a wide variety of neurons and muscles in a rapid and straightforward manner. For this, we paired nanoinjection of compounds with electrophysiological recordings from the Giant Fiber System of Drosophila melanogaster, which mediates the escape response of the fly.
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Date Issued: 2013
PURL: http://purl.flvc.org/fcla/dt/3362560
Subject Headings: Drosophila melanogaster, Genetics, Drosophila melanogaster, Life cycles, Insects, Physiology, Developmental neurobiology, Neural transmission, Cholinergic mechanisms
Format: Document (PDF)

Title: Frazzled’s Role in Synapse Formation at a Drosophila Giant Synapse.
Creator: Lopez, Juan, Murphey, Rodney K., Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: In Drosophila melanogaster, the GFS is synaptically coupled to the Tergotrochanteral motoneurons; these neurons form a signaling pathway from the brain to the jump muscles (Thomas and Wyman, 1983). Part of this signaling is done through gap junctions, and placement of these gap junctions was partially shown to be regulated by the binding of Netrin, a class of guidance molecule (Orr et al., 2014). In the present study we investigate the role of Netrin's receptor Frazzled in the placement of...
Show moreIn Drosophila melanogaster, the GFS is synaptically coupled to the Tergotrochanteral motoneurons; these neurons form a signaling pathway from the brain to the jump muscles (Thomas and Wyman, 1983). Part of this signaling is done through gap junctions, and placement of these gap junctions was partially shown to be regulated by the binding of Netrin, a class of guidance molecule (Orr et al., 2014). In the present study we investigate the role of Netrin's receptor Frazzled in the placement of gap junctions in Drosophila at: 1) Presynaptic neurons (Giant Fibers [GF]), 2) Postsynaptic neurons (Tergotrochanteral motoneurons [TTMn]), and 3) Presynaptic + Postsynaptic neurons simultaneously. Effects of Frazzled were tested using Frazzled RNAi and a combination of electrophysiological recordings and imaging of the GF-TTMn synapse. The results from this study show that presynaptic and postsynaptic knockdown of Frazzled delayed muscular responses and altered the anatomy of both the GF's and TTMn's.
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Date Issued: 2018
PURL: http://purl.flvc.org/fau/fd/FA00013085
Subject Headings: Drosophila melanogaster--Nervous system., Gap Junctions., Synapses., Netrin Receptors.
Format: Document (PDF)

Title: HISTAMINERGIC AND NOCICEPTIVE GROOMING IN DROSOPHILA MELANOGASTER: AN ANALYSIS OF THE MOLECULAR MECHANISMS AND A BEHAVIORAL RESPONSE TO NOXIOUS CHEMICAL STIMULI.
Creator: John, Ciny, Dawson-Scully, Ken, Murphey, Rodney, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: Insect grooming has various functions, including defense against parasites and pathogens, cleaning of dust particles, and maintenance of sensory receptors. The hierarchy of grooming behavior suggests that cleaning one body part is more crucial than the other, the priority order more specifically being eyes, antennae, abdomen, then wings, followed by the thorax. Histamine is an extensively studied neurotransmitter found in the central nervous system of many animals. In Drosophila, histamine is...
Show moreInsect grooming has various functions, including defense against parasites and pathogens, cleaning of dust particles, and maintenance of sensory receptors. The hierarchy of grooming behavior suggests that cleaning one body part is more crucial than the other, the priority order more specifically being eyes, antennae, abdomen, then wings, followed by the thorax. Histamine is an extensively studied neurotransmitter found in the central nervous system of many animals. In Drosophila, histamine is found in both the peripheral and central nervous systems and is necessary for visual and mechanosensory behaviors. Histamine-gated chloride channel 1 (HisCl1) and Ora transientless (Ort) are two characterized histamine receptors, both of which are vital for visual signaling in the fly.
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Date Issued: 2019
PURL: http://purl.flvc.org/fau/fd/FA00013321
Subject Headings: Drosophila melanogaster, Grooming behavior in animals, Nociception, Histaminergic mechanisms
Format: Document (PDF)

Title: The Effects of MsrA and MsrB in Anoxia Tolerance in Aging Drosophila melanogaster.
Creator: Suthakaran, Nirthieca, Binninger, David, Florida Atlantic University, Charles E. Schmidt College of Medicine, Department of Biomedical Sciences
Abstract/Description: Drosophila melanogaster tolerates several hours of anoxia (the absence of oxygen) by entering a protective coma. A burst of reactive oxygen species (ROS) is produced when oxygen is reintroduced to the cells. ROS causes oxidative damage to critical cellular molecules, which contribute to aging and development of certain agerelated conditions. The amino acid, methionine, is susceptible to oxidation, although this damage can be reversed by methionine sulfoxide reductases (Msr). This project...
Show moreDrosophila melanogaster tolerates several hours of anoxia (the absence of oxygen) by entering a protective coma. A burst of reactive oxygen species (ROS) is produced when oxygen is reintroduced to the cells. ROS causes oxidative damage to critical cellular molecules, which contribute to aging and development of certain agerelated conditions. The amino acid, methionine, is susceptible to oxidation, although this damage can be reversed by methionine sulfoxide reductases (Msr). This project investigates the effect of Msr-deficiency on anoxia tolerance in Drosophila throughout the lifespan of the animal. The data show that the time for recovery from the protective comma as well as the survival of the animals lacking any Msr activity depends on how quickly the coma is induced by the anoxic conditions. Insight into the roles(s) of Msr genes under anoxic stress can lead us to a path of designing therapeutic drugs around these genes in relation to stroke.
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Date Issued: 2018
PURL: http://purl.flvc.org/fau/fd/FA00013046
Subject Headings: Drosophila melanogaster, Methionine Sulfoxide Reductases, Anoxia, Aging, Oxidative stress
Format: Document (PDF)

Title: Peptidomic analysis and characterization of the venom from Conus purpurascens.
Creator: Rodriguez, Alena, Mari, Frank, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description: The venom of cone snails is a potent cocktail of peptides, proteins, and other small molecules. Several of the peptides (conopeptides and conotoxins) target ion channels and receptors and have proven useful as biochemical probes or pharmaceutical leads. In this study, the venom of a fish-hunting cone snail, Conus purpurascens was analyzed for intraspecific variability; α-conotoxins from the venom were isolated by high performance liquid chromatography, identified by mass spectrometry and...
Show moreThe venom of cone snails is a potent cocktail of peptides, proteins, and other small molecules. Several of the peptides (conopeptides and conotoxins) target ion channels and receptors and have proven useful as biochemical probes or pharmaceutical leads. In this study, the venom of a fish-hunting cone snail, Conus purpurascens was analyzed for intraspecific variability; α-conotoxins from the venom were isolated by high performance liquid chromatography, identified by mass spectrometry and nuclear magnetic resonance, and tested in a electrophysiological assay in Drosophila melanogaster; the effects of diet change on venom composition was investigated. It has been determined that each specimen of C. purpurascens expresses a distinct venom, resulting in the expression of more than 5,000 unique conopeptides across the species. α- conotoxin PIA was shown to inhibit the Dα7 nicotinic acetylcholine receptor.
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Date Issued: 2015
PURL: http://purl.flvc.org/fau/fd/FA00004403, http://purl.flvc.org/fau/fd/FA00004403
Subject Headings: Conidae -- Environmental aspects, Drosophila melanogaster, Gastropoda -- Venom, Peptides -- Structure, Venom
Format: Document (PDF)

Title: Characterization of Group B Sox genes in the development of Drosophila nervous system.
Creator: Singh, Shweta, Dawson-Scully, Ken, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: Sox proteins all contain a single ~70 amino acid High Mobility Group (HMG) DNA-binding domain with strong homology to that of Sry, the mammalian testisdetermining factor. In Drosophila melanogaster, there are four closely related members of the B group, Dichaete (D), Sox Neuro (Sox N), Sox 21a, and Sox 21b that each exhibit ~90% sequence identity within the HMG domain.The previous study has shown that Dichaete plays a major role in embryonic nervous system development and is expressed in...
Show moreSox proteins all contain a single ~70 amino acid High Mobility Group (HMG) DNA-binding domain with strong homology to that of Sry, the mammalian testisdetermining factor. In Drosophila melanogaster, there are four closely related members of the B group, Dichaete (D), Sox Neuro (Sox N), Sox 21a, and Sox 21b that each exhibit ~90% sequence identity within the HMG domain.The previous study has shown that Dichaete plays a major role in embryonic nervous system development and is expressed in several clusters of neurons in the brain, including intermingled olfactory LNs and central-complex neurons strongly expressed in local interneuron of the olfactory system. However, little is known about the possible expression and functions of the related group B Sox genes in the larval and adult brain. In particular, it is unclear if Sox N may function along with Dichaete in controlling the development or physiology of the adult olfactory system. Our data suggests Sox N potential role in the elaboration of the olfactory circuit formation.
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Date Issued: 2017
PURL: http://purl.flvc.org/fau/fd/FA00004907, http://purl.flvc.org/fau/fd/FA00004907
Subject Headings: Drosophila melanogaster--Physiology., Transcription factors., Gene expression., Genetic transcription., Cell cycle., Neural stem cells.
Format: Document (PDF)

Title: Developmental delays in methionine sulfoxide reductase mutants in Drosophila Melanogaster.
Creator: Hausman, William, Binninger, David, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: Aging is a biological process that has many detrimental effects due to the accumulation of oxidative damage to key biomolecules due to the action of free radicals. Methionine sulfoxide reductase (Msr) functions to repair oxidative damage to methionine residues. Msr comes in two forms, MsrA and MsrB, each form has been shown to reduce a specific enantiomer of bound and free oxidized methionine. Effects of Msr have yet to be studied in the major developmental stages of Drosophila melanogaster...
Show moreAging is a biological process that has many detrimental effects due to the accumulation of oxidative damage to key biomolecules due to the action of free radicals. Methionine sulfoxide reductase (Msr) functions to repair oxidative damage to methionine residues. Msr comes in two forms, MsrA and MsrB, each form has been shown to reduce a specific enantiomer of bound and free oxidized methionine. Effects of Msr have yet to be studied in the major developmental stages of Drosophila melanogaster despite the enzymes elevated expression during these stages. A developmental timeline was determined for MsrA mutant, MsrB mutant, and double null mutants against a wild type control. Results show that the Msr double mutant is delayed approximately 20 hours in the early/mid third instar stage while each of the single mutants showed no significant difference to the wild type. Data suggests that the reasoning of this phenomenon is due to an issue gaining mass.
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Date Issued: 2014
PURL: http://purl.flvc.org/fau/fd/FA00004200, http://purl.flvc.org/fau/fd/FA00004200
Subject Headings: Aging -- Molecular aspects, Cellular signal transduction, Drosophila melanogaster -- Genetics, Mitochondrial pathology, Mutation (Biology), Oxidative stress
Format: Document (PDF)

Title: Functional roles of L1-Cam/Neuroglian in the nervous system of Drosophila Melanogaster.
Creator: Kudumala, Sirisha, Godenschwege, Tanja A., Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: Neuronal cell adhesion molecules of L1 family play a critical role in proper nervous system development. Various mutations on human L1-CAM that lead to severe neurodevelopmental disorders like retardation, spasticity etc. termed under L1 syndrome. The vertebrr their roles in axon pathfinding, neurite extension and cell migration, howeverate L1CAM and its homolog in Drosophila, neuroglian (nrg) have been well studied fo, much less is known about the mechanisms by which they fine tune synaptic...
Show moreNeuronal cell adhesion molecules of L1 family play a critical role in proper nervous system development. Various mutations on human L1-CAM that lead to severe neurodevelopmental disorders like retardation, spasticity etc. termed under L1 syndrome. The vertebrr their roles in axon pathfinding, neurite extension and cell migration, howeverate L1CAM and its homolog in Drosophila, neuroglian (nrg) have been well studied fo, much less is known about the mechanisms by which they fine tune synaptic connectivity to control the development and maintenance of synaptic connections within neuronal circuits. Here we characterized the essential role of nrg in regulating synaptic structure and function in vivo in a well characterized Drosophila central synapse model neuron, the Giant Fiber (GF) system. Previous studies from our lab revealed that the phosphorylation status of the tyrosine in the Ankyrin binding FIGQY motif in the intracellular domain of Nrg iscrucial for synapse formation of the GF to Tergo-Trochanteral Motor neuron (TTMn) synapse in the GF circuit. The present work provided us with novel insights into the role of Nrg-Ank interaction in regulating Nrg function during synapse formation and maintenance. By utilizing a sophisticated Pacman based genomic rescue strategy we have shown that dynamic regulation of the Neuroglian–Ankyrin interaction is required to coordinate transsynaptic development in the GF–TTMn synapse. In contrast, the strength of Ankyrin binding directly controls the balance between synapse formation and maintenance at the NMJ. Human L1 pathological mutations affect different biological processes distinctively and thus their proper characterization in vivo is essential to understand L1CAM function. By utilizing nrg14;P[nrg180ΔFIGQY] mutants that have exclusive synaptic defects and the previously characterized nrg849 allele that affected both GF guidance and synaptic function, we were able to analyze pathological L1CAM missense mutations with respect to their effects on guidance and synapse formation in vivo. We found that the human pathological H210Q, R184Q and Y1070C, but not the E309K and L120V L1CAM mutations affect outside-in signaling via the FIGQY Ankyrin binding domain which is required for synapse formation and not for axon guidance while L1CAM homophilic binding and signaling via the ERM motif is essential for axon guidance in Drosophila.
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Date Issued: 2014
PURL: http://purl.flvc.org/fau/fd/FA00004131, http://purl.flvc.org/fau/fd/FA00004131
Subject Headings: Cell adhesion molecules, Cellular signal transduction, Cognitive neuroscience, Cognitive neuroscience, Drosophila melanogaster, Molecular neurobiology
Format: Document (PDF)

Title: Functional Stress Resistance: The Role of Protein Kinase G in Modulating Neuronal Excitability in Caenorhabditis Elegans and Drosophila Melanogaster.
Creator: Kelly, Stephanie Suzanne, Dawson-Scully, Ken, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: Diseases such as epilepsy, pain, and neurodegenerative disorders are associated with changes in neuronal dysfunction due to an imbalance of excitation and inhibition. This work details a novel electroconvulsive seizure assay for C. elegans using the well characterized cholinergic and GABAergic excitation and inhibition of the body wall muscles and the resulting locomotion patterns to better understand neuronal excitability. The time to recover normal locomotion from an electroconvulsive...
Show moreDiseases such as epilepsy, pain, and neurodegenerative disorders are associated with changes in neuronal dysfunction due to an imbalance of excitation and inhibition. This work details a novel electroconvulsive seizure assay for C. elegans using the well characterized cholinergic and GABAergic excitation and inhibition of the body wall muscles and the resulting locomotion patterns to better understand neuronal excitability. The time to recover normal locomotion from an electroconvulsive seizure could be modulated by increasing and decreasing inhibition. GABAergic deficits and a chemical proconvulsant resulted in an increased recovery time while anti-epileptic drugs decreased seizure duration. Successful modulation of excitation and inhibition in the new assay led to the investigation of a cGMP-dependent protein kinase (PKG) which modulates potassium (K+) channels, affecting neuronal excitability, and determined that increasing PKG activity decreases the time to recovery from an electroconvulsive seizure. The new assay was used as a forward genetic screening tool using C. elegans and several potential genes that affect seizure susceptibility were found to take longer to recover from a seizure. A naturally occurring polymorphism for PKG in D. melanogaster confirmed that both genetic and pharmacological manipulation of PKG influences seizure duration. PKG has been implicated in stress tolerance, which can be affected by changes in neuronal excitability associated with aging, so stress tolerance and locomotor behavior in senescent flies was investigated. For the first time, PKG has been implicated in aging phenotypes with high levels of PKG resulting in reduced locomotion and lifespan in senescent flies. The results suggest a potential new role for PKG in seizure susceptibility and aging.
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Date Issued: 2019
PURL: http://purl.flvc.org/fau/fd/FA00013225
Subject Headings: Caenorhabditis elegans, Drosophila melanogaster, Cyclic GMP-Dependent Protein Kinases, Seizures
Format: Document (PDF)

Title: Synaptic Rearrangements and the Role of Netrin-Frazzled Signaling in Shaping the Drosophila Giant Fiber Circuit.
Creator: Lloyd, Brandon N., Murphey, Rodney K., Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: In the developing CNS, presynaptic neurons often have exuberant overgrowth and form excess (and overlapping) postsynaptic connections. Importantly, these excess connections are refined during circuit maturation so that only the appropriate connections remain. This synaptic rearrangement phenomenon has been studied extensively in vertebrates but many of those models involve complex neuronal circuits with multiple presynaptic inputs and postsynaptic outputs. Using a simple escape circuit in...
Show moreIn the developing CNS, presynaptic neurons often have exuberant overgrowth and form excess (and overlapping) postsynaptic connections. Importantly, these excess connections are refined during circuit maturation so that only the appropriate connections remain. This synaptic rearrangement phenomenon has been studied extensively in vertebrates but many of those models involve complex neuronal circuits with multiple presynaptic inputs and postsynaptic outputs. Using a simple escape circuit in Drosophila melanogaster (the giant fiber circuit), we developed tools that enabled us to study the molecular development of this circuit; which consists of a bilaterally symmetrical pair of presynaptic interneurons and postsynaptic motorneurons. In the adult circuit, each presynaptic interneuron (giant fiber) forms a single connection with the ipsilateral, postsynaptic motorneuron (TTMn). Using new tools that we developed we labeled both giant fibers throughout their development and saw that these neurons overgrew their targets and formed overlapping connections. As the circuit matured, giant fibers pruned their terminals and refined their connectivity such that only a single postsynaptic connection remained with the ipsilateral target. Furthermore, if we ablated one of the two giant fibers during development in wildtype animals, the remaining giant fiber often retained excess connections with the contralateral target that persisted into adulthood. After demonstrating that the giant fiber circuit was suitable to study synaptic rearrangement, we investigated two proteins that might mediate this process. First, we were able to prevent giant fibers from refining their connectivity by knocking out highwire, a ubiquitin ligase that prevented pruning. Second, we investigated whether overexpressing Netrin (or Frazzled), part of a canonical axon guidance system, would affect the refinement of giant fiber connectivity. We found that overexpressing Netrin (or Frazzled) pre- & postsynaptically resulted in some giant fibers forming or retaining excess connections, while exclusively presynaptic (or postsynaptic) expression of either protein had no effect. We further showed that by simultaneously reducing (Slit-Robo) midline repulsion and elevating Netrin (or Frazzled) pre- & postsynaptically, we significantly enhanced the proportion of giant fibers that formed excess connections. Our findings suggest that Netrin-Frazzled and Slit-Robo signaling play a significant role in refining synaptic circuits and shaping giant fiber circuit connectivity.
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Date Issued: 2016
PURL: http://purl.flvc.org/fau/fd/FA00004758, http://purl.flvc.org/fau/fd/FA00004758
Subject Headings: Drosophila melanogaster--Cytogenetics., Genetic transcription., Transcription factors., Cellular signal transduction., Cellular control mechanisms., Cell receptors.
Format: Document (PDF)

Title: Highwire coordinates synapse formation and maturation by regulating both a map kinase cascade and the ability of the axon to respond to external cues in the giant fiber system of Drosophila Melanogaster.
Creator: Borgen, Melissa A., Murphey, Rodney K., Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: The ubiquitin ligase Highwire is responsible for cell-autonomously promoting synapse formation in the Drosophila Giant Fiber system. highwire mutants show defects in synaptic function and extra branching at the axon terminal, corresponding to transient branching that occur in the course of giant synapse formation during metamorphosis. The MAP kinase pathway, including Wallenda and JNK/Basket, plus the transcription factor Jun, act to suppress synaptic function and axon pruning in a dosage...
Show moreThe ubiquitin ligase Highwire is responsible for cell-autonomously promoting synapse formation in the Drosophila Giant Fiber system. highwire mutants show defects in synaptic function and extra branching at the axon terminal, corresponding to transient branching that occur in the course of giant synapse formation during metamorphosis. The MAP kinase pathway, including Wallenda and JNK/Basket, plus the transcription factor Jun, act to suppress synaptic function and axon pruning in a dosage sensitive manner, suggesting different molecular mechanisms downstream of the MAP kinase pathway govern function and pruning. A novel role for Highwire is revealed, regulating the giant fiber axon’s ability to respond to external cues regulated by Fos. When expression of the transcription factor Fos is disrupted in the post-synaptic TTMn or surrounding midline glia of highwire mutants, the giant fiber axons show a marked increase in axon overgrowth and midline crossing. However, synaptic function is rescued by the cell nonautonomous manipulation of Fos, indicating distinct mechanisms downstream of Highwire regulating synaptic function and axon morphology.
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Date Issued: 2014
PURL: http://purl.flvc.org/fau/fd/FA00004081, http://purl.flvc.org/fau/fd/FA00004081
Subject Headings: Cell differentiation, Cellular control mechanisms, Cellular signal transduction, Drosophila melanogaster -- Cytogenetics, Gene expression, Genetic transcription
Format: Document (PDF)

FAU Theses and Dissertations (32)	+ -
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Drosophila melanogaster (22)	+ -
Cellular signal transduction (12)	+ -
Genetic transcription (7)	+ -
Cytogenetics (5)	+ -
Gene expression (5)	+ -

Mutation (Biology) (5)	+ -
Oxidative stress (5)	+ -
Transcription factors (5)	+ -
Cellular signal transduction. (4)	+ -
Mitochondrial pathology (4)	+ -
Regulation (4)	+ -
Transcription factors. (4)	+ -
Cellular control mechanisms (3)	+ -
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Cellular control mechanisms. (2)	+ -
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Charles E. Schmidt College of Science (31)	+ -
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Florida Atlantic University (23)	+ -
Binninger, David (8)	+ -
Dawson-Scully, Ken (6)	+ -

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