Coral Warr

A New Role for Neuropeptide F Signaling in Controlling Developmental Timing and Body Size in Drosophila melanogaster

Publisher: Oxford University Press (OUP)

Date: 09-2020

DOI: 10.1534/GENETICS.120.303475

Abstract: As juvenile animals grow, their behavior, physiology, and development need to be matched to environmental conditions to ensure they survive to adulthood. However, we know little about how behavior and physiology are integrated with development to achieve this outcome. Neuropeptides are prime candidates for achieving this due to their well-known signaling functions in controlling many aspects of behavior, physiology, and development in response to environmental cues. In the growing Drosophila larva, while several neuropeptides have been shown to regulate feeding behavior, and a handful to regulate growth, it is unclear if any of these play a global role in coordinating feeding behavior with developmental programs. Here, we demonstrate that Neuropeptide F Receptor (NPFR), best studied as a conserved regulator of feeding behavior from insects to mammals, also regulates development in Drosophila. Knocking down NPFR in the prothoracic gland, which produces the steroid hormone ecdysone, generates developmental delay and an extended feeding period, resulting in increased body size. We show that these effects are due to decreased ecdysone production, as these animals have reduced expression of ecdysone biosynthesis genes and lower ecdysone titers. Moreover, these phenotypes can be rescued by feeding larvae food supplemented with ecdysone. Further, we show that NPFR negatively regulates the insulin signaling pathway in the prothoracic gland to achieve these effects. Taken together, our data demonstrate that NPFR signaling plays a key role in regulating animal development, and may, thus, play a global role in integrating feeding behavior and development in Drosophila.

Functional and molecular evolution of olfactory neurons and receptors for aliphatic esters across the Drosophila genus

Publisher: Springer Science and Business Media LLC

Date: 24-12-2009

DOI: 10.1007/S00359-009-0496-6

Abstract: Insect olfactory receptor (Or) genes are large, rapidly evolving gene families of considerable interest for evolutionary studies. They determine the responses of sensory neurons which mediate critical behaviours and ecological adaptations. We investigated the evolution across the genus Drosophila of a subfamily of Or genes largely responsible for the perception of ecologically relevant aliphatic esters products of yeast fermentation and fruits. Odour responses were recorded from eight classes of olfactory receptor neurons known to express this Or subfamily in D. melanogaster and from homologous sensilla in seven other species. Despite the fact that these species have erged over an estimated 40 million years, we find that odour specificity is largely maintained in seven of the eight species. In contrast, we observe extensive changes in most neurons of the outgroup species D. virilis, and in two neurons across the entire genus. Some neurons show small shifts in specificity, whilst some dramatic changes correlate with gene duplication or loss. An olfactory receptor neuron response similarity tree did not match an Or sequence similarity tree, but by aligning Or proteins of likely functional equivalence we identify residues that may be relevant for odour specificity. This will inform future structure-function studies of Drosophila Ors.

A role for the Drosophila zinc transporter Zip88E in protecting against dietary zinc toxicity

Publisher: Public Library of Science (PLoS)

Date: 13-07-2017

DOI: 10.1371/JOURNAL.PONE.0181237

High resolution structure of cleaved Serpin 42 da from Drosophila melanogaster

Publisher: Springer Science and Business Media LLC

Date: 24-04-2014

DOI: 10.1186/1472-6807-14-14

Molecular basis of female-specific odorant responses in Bombyx mori

Publisher: Elsevier BV

Date: 03-2009

DOI: 10.1016/J.IBMB.2008.11.002

Abstract: Males and females of many moth species exhibit important differences in sexual behaviours. Much research in this field has focused on the male-specific behaviour, electrophysiology and molecular biology of sex pheromone reception. Female-specific behaviours have been less well studied although, like male-specific behaviours, they could provide opportunities for intervention and management of lepidopteran pests. Previously, we identified genes encoding putative odorant receptors (ORs) from the genome of the silkworm, Bombyx mori, some of which have higher levels of steady-state transcript in the antennae of adult females compared with males. We have identified the full-length cDNA sequences of some of these ORs and described a novel OR that is part of a female-biased clade. Using expression in Sf9 cells and a calcium-imaging assay, we tested a range of compounds for their ability to activate the most highly female-biased ORs, BmOR19, BmOR30, BmOR45 and BmOR47. BmOR19 responds to linalool, while BmOR45 and BmOR47 respond to benzoic acid > 2-phenylethanol > benzaldehyde. No activating ligands were found for BmOR30. RNA in situ hybridisation experiments reveal that BmOR19 is expressed in female olfactory sensory neurons that are co-located in the same sensilla as a second ORN expressing BmOR45 and/or BmOR47. Taken together the activity and expression of these receptors is likely explanatory of the observed electrophysiology of long sensilla trichoidea of female B. mori, previously shown to each contain one terpene (BmOR19) and one benzoic acid (BmOR45, BmOR47) sensory neuron. Plant volatiles such as linalool, benzoic acid, 2-phenylethanol and benzaldehyde are oviposition cues for females of some moths. These compounds have also been found in male-produced pheromone blends extracted from the hair pencils of many noctuid species. Hair pencil structures have not previously been reported for B. mori, but we have found hair pencil-like structures in adult male B. mori that are absent in female moths. It is proposed that BmOR19, BmOR45 and BmOR47 account for some of the female-specific odorant responses in B. mori, such as oviposition and/or detection of an as yet unidentified male-produced sex pheromone.

Capturing embryonic development from metamorphosis: how did the terminal patterning signalling pathway of Drosophila evolve?

Publisher: Elsevier BV

Date: 07-2014

DOI: 10.1016/J.COIS.2014.04.007

Detection of Volatile Indicators of Illicit Substances by the Olfactory Receptors of Drosophila melanogaster

Publisher: Oxford University Press (OUP)

Date: 07-06-2010

DOI: 10.1093/CHEMSE/BJQ050

Dock/Nck facilitates PTP61F/PTP1B regulation of insulin signalling

Publisher: Portland Press Ltd.

Date: 14-09-2011

DOI: 10.1042/BJ20110799

Abstract: PTP1B (protein tyrosine phosphatase 1B) is a negative regulator of IR (insulin receptor) activation and glucose homoeostasis, but the precise molecular mechanisms governing PTP1B substrate selectivity and the regulation of insulin signalling remain unclear. In the present study we have taken advantage of Drosophila as a model organism to establish the role of the SH3 (Src homology 3)/SH2 adaptor protein Dock (Dreadlocks) and its mammalian counterpart Nck in IR regulation by PTPs. We demonstrate that the PTP1B orthologue PTP61F dephosphorylates the Drosophila IR in S2 cells in vitro and attenuates IR-induced eye overgrowth in vivo. Our studies indicate that Dock forms a stable complex with PTP61F and that Dock/PTP61F associate with the IR in response to insulin. We report that Dock is required for effective IR dephosphorylation and inactivation by PTP61F in vitro and in vivo. Furthermore, we demonstrate that Nck interacts with PTP1B and that the Nck/PTP1B complex inducibly associates with the IR for the attenuation of IR activation in mammalian cells. Our studies reveal for the first time that the adaptor protein Dock/Nck attenuates insulin signalling by recruiting PTP61F/PTP1B to its substrate, the IR.

In vivo zinc toxicity phenotypes provide a sensitized background that suggests zinc transport activities for most of the Drosophila Zip and ZnT genes

Publisher: Springer Science and Business Media LLC

Date: 17-01-2013

DOI: 10.1007/S00775-013-0976-6

Abstract: Members of the ZIP (SLC39A) and ZnT (SLC30A) families of transmembrane domain proteins are predicted to transport the essential transition metal zinc across membranes, regulating cellular zinc content and distribution via uptake and efflux at the outer plasma and organellar membranes. Twenty-four ZIP and ZnT proteins are encoded in mammalian genomes, raising questions of whether all actually transport zinc, whether several function together in the same tissues/cell types, and how the activity of these transporters is coordinated. To address these questions, we have taken advantage of the ability to manipulate several genes simultaneously in targeted cell types in Drosophila. Previously we reported zinc toxicity phenotypes caused by combining overexpression of a zinc uptake gene, dZip42C.1, with suppression of a zinc efflux gene, dZnT63C. Here we show that these phenotypes can be used as a sensitized in vivo system to detect subtle alterations in zinc transport activity that would be buffered in healthy cells. Using two adult tissues, the fly eye and midline (thorax/abdomen), we find that when overexpressed, most of the 17 Drosophila Zip and ZnT genes modify the zinc toxicity phenotypes in a manner consistent with their predicted zinc transport activity. In most cases, we can reconcile that activity with the cellular localization of an enhanced green fluorescent protein tagged version of the protein. Additionally, targeted suppression of each gene by RNA interference reveals several of the fly Zip and ZnT genes are required in the eye, indicating that numerous independent zinc transport genes are acting together in a single tissue.

Insulin-like signalling influences the coordination of larval hemocyte number with body size in Drosophila melanogaster

Publisher: Oxford University Press (OUP)

Date: 07-2020

DOI: 10.1534/G3.120.401313

Abstract: Blood cells, known as hemocytes in invertebrates, play important and conserved roles in immunity, wound healing and tissue remodelling. The control of hemocyte number is therefore critical to ensure these functions are not compromised, and studies using Drosophila melanogaster are proving useful for understanding how this occurs. Recently, the embryonic patterning gene, torso-like (tsl), was identified as being required both for normal hemocyte development and for providing immunity against certain pathogens. Here, we report that Tsl is required specifically during the larval phase of hematopoiesis, and that tsl mutant larvae likely have reduced hemocyte numbers due to a reduced larval growth rate and compromised insulin signaling. Consistent with this, we find that impairing insulin-mediated growth, either by nutrient deprivation or genetically, results in fewer hemocytes. This is likely the result of impaired insulin-like signaling in the hemocytes themselves, since modulation of Insulin-like Receptor (InR) activity specifically in hemocytes causes concomitant changes to their population size in developing larvae. Taken together, our work reveals the strong relationship that exists between body size and hemocyte number, and suggests that insulin-like signaling contributes to, but is not solely responsible for, keeping these tightly aligned during larval development.

Genome-Wide Screen for New Components of the Drosophila melanogaster Torso Receptor Tyrosine Kinase Pathway

Publisher: Oxford University Press (OUP)

Date: 03-2018

DOI: 10.1534/G3.117.300491

Abstract: Patterning of the Drosophila embryonic termini by the Torso (Tor) receptor pathway has long served as a valuable paradigm for understanding how receptor tyrosine kinase signaling is controlled. However, the mechanisms that underpin the control of Tor signaling remain to be fully understood. In particular, it is unclear how the Perforin-like protein Torso-like (Tsl) localizes Tor activity to the embryonic termini. To shed light on this, together with other aspects of Tor pathway function, we conducted a genome-wide screen to identify new pathway components that operate downstream of Tsl. Using a set of molecularly defined chromosomal deficiencies, we screened for suppressors of ligand-dependent Tor signaling induced by unrestricted Tsl expression. This approach yielded 59 genomic suppressor regions, 11 of which we mapped to the causative gene, and a further 29 that were mapped to & genes. Of the identified genes, six represent previously unknown regulators of embryonic Tor signaling. These include twins (tws), which encodes an integral subunit of the protein phosphatase 2A complex, and α-tubulin at 84B (αTub84B), a major constituent of the microtubule network, suggesting that these may play an important part in terminal patterning. Together, these data comprise a valuable resource for the discovery of new Tor pathway components. Many of these may also be required for other roles of Tor in development, such as in the larval prothoracic gland where Tor signaling controls the initiation of metamorphosis.

A Novel Family of Divergent Seven-Transmembrane Proteins

Publisher: Elsevier BV

Date: 02-1999

DOI: 10.1016/S0896-6273(00)81093-4

Abstract: Although insects have proven to be valuable models for exploring the function, organization, and development of the olfactory system, the receptor molecules that bind odors have not been identified in any insect. We have developed a novel search algorithm, used it to search the Drosophila genomic sequence database, and identified a large multigene family encoding seven transmembrane domain proteins that are expressed in olfactory organs. We show that expression is restricted to subsets of olfactory receptor neurons (ORNs) for a number of these genes. Different members of the family initiate expression at different times during antennal development. Some of the genes are not expressed in a mutant of the Acj6 POU-domain transcription factor, a mutant in which a subset of ORNs show abnormal odorant specificities.

Trunk cleavage is essential for Drosophila terminal patterning and can occur independently of Torso-like

Publisher: Springer Science and Business Media LLC

Date: 03-03-2014

DOI: 10.1038/NCOMMS4419

Abstract: Terminal patterning in Drosophila is governed by a localized interaction between the Torso kinase (Tor) and its ligand Trunk (Trk). Currently, it is proposed that Trk must be cleaved in order to bind Tor, and that these proteolytic events are controlled by secretion of Torso-like (Tsl) only at the embryo poles. However, controversy surrounds these ideas since neither cleaved Trk nor a protease that functions in terminal patterning have been identified. Here we show that Trk is cleaved multiple times in vivo and that these proteolytic events are essential for its function. Unexpectedly, however, the Trk cleavage patterns we observe are unaltered in tsl-null mutants. One explanation for these data is that the influence of Tsl on localized Trk cleavage at the embryo poles is subtle and cannot be readily detected. Alternatively, we favour a scenario where Tsl functions post proteolytic processing of Trk to control localized terminal patterning.

The Drosophila melanogaster Phospholipid Flippase dATP8B Is Required for Odorant Receptor Function

Publisher: Public Library of Science (PLoS)

Date: 20-03-2014

DOI: 10.1371/JOURNAL.PGEN.1004209

A Unified Nomenclature System for the Drosophila Odorant Receptors

Publisher: Elsevier BV

Date: 07-2000

DOI: 10.1016/S0092-8674(00)00020-9

Neuropeptide F receptor acts in the Drosophila prothoracic gland to regulate growth and developmental timing

Publisher: Cold Spring Harbor Laboratory

Date: 17-12-2019

DOI: 10.1101/2019.12.16.878967

Abstract: As juvenile animals grow, their behaviour, physiology, and development need to be matched to environmental conditions to ensure they survive to adulthood. However, we know little about how behaviour and physiology are integrated with development to achieve this outcome. Neuropeptides are prime candidates for achieving this due to their well-known signalling functions in controlling many aspects of behaviour, physiology and development in response to environmental cues. In the growing Drosophila larva, while several neuropeptides have been shown to regulate feeding behaviour, and a handful to regulate growth, it is unclear if any of these play a global role in coordinating feeding behaviour with developmental programs. Here, we demonstrate that Neuropeptide F Receptor (NPFR), best studied as a conserved regulator of feeding behaviour from insects to mammals, also regulates development in Drosophila . Knocking down NPFR in the prothoracic gland, which produces the steroid hormone ecdysone, generates developmental delay and an extended feeding period, resulting in increased body size. We show that these effects are due to decreased ecdysone production, as these animals have reduced expression of ecdysone biosynthesis genes and lower ecdysone titres. Moreover, these phenotypes can be rescued by feeding larvae food supplemented with ecdysone. Further, we show that NPFR negatively regulates the insulin signalling pathway in the prothoracic gland to achieve these effects. Taken together, our data demonstrate that NPFR signalling plays a key role in regulating animal development and may thus play a global role in integrating feeding behaviour and development in Drosophila .

Natural variation at the Drosophila melanogaster Or22 odorant receptor locus is associated with changes in olfactory behaviour.

Publisher: The Royal Society

Date: 09-2021

DOI: 10.1098/RSOB.210158

Abstract: In insects, many critical olfactory behaviours are mediated by the large odorant receptor ( Or ) gene family, which determines the response properties of different classes of olfactory receptor neurons (ORNs). While ORN responses are generally conserved within and between Drosophila species, variant alleles of the D. melanogaster Or22 locus have previously been shown to alter the response profile of an ORN class called ab3A. These alleles show potential clinal variation, suggesting that selection is acting at this locus. Here, we investigated if the changes seen in ab3A responses lead to changes in olfactory-related behaviours. We show that variation at the Or22 locus and in the ab3A neurons are not fully compensated for by other ORNs and lead to overall changes in antennal odorant detection. We further show that this correlates with differences in odorant preference behaviour and with differences in oviposition site preference, with flies that have the chimaeric short allele strongly preferring to oviposit on banana. These findings indicate that variation at the Or22 locus leads to changes in olfactory-driven behaviours, and add support to the idea that the ab3A neurons are of especial importance to the ecology of Drosophila flies.

A cis-regulatory-directed pipeline for the identification of genes involved in cardiac development and disease.

Publisher: Springer Science and Business Media LLC

Date: 12-2021

DOI: 10.1186/S13059-021-02539-0

Abstract: Congenital heart diseases are the major cause of death in newborns, but the genetic etiology of this developmental disorder is not fully known. The conventional approach to identify the disease-causing genes focuses on screening genes that display heart-specific expression during development. However, this approach would have discounted genes that are expressed widely in other tissues but may play critical roles in heart development. We report an efficient pipeline of genome-wide gene discovery based on the identification of a cardiac-specific cis -regulatory element signature that points to candidate genes involved in heart development and congenital heart disease. With this pipeline, we retrieve 76% of the known cardiac developmental genes and predict 35 novel genes that previously had no known connectivity to heart development. Functional validation of these novel cardiac genes by RNAi-mediated knockdown of the conserved orthologs in Drosophila cardiac tissue reveals that disrupting the activity of 71% of these genes leads to adult mortality. Among these genes, RpL14 , RpS24 , and Rpn8 are associated with heart phenotypes. Our pipeline has enabled the discovery of novel genes with roles in heart development. This workflow, which relies on screening for non-coding cis -regulatory signatures, is amenable for identifying developmental and disease genes for an organ without constraining to genes that are expressed exclusively in the organ of interest.

The toll and Imd pathways are not required for wolbachia-mediated dengue virus interference.

Publisher: American Society for Microbiology

Date: 11-2013

DOI: 10.1128/JVI.01522-13

Abstract: Wolbachia blocks dengue virus replication in Drosophila melanogaster as well as in Aedes aegypti . Using the Drosophila model and mutations in the Toll and Imd pathways, we showed that neither pathway is required for expression of the dengue virus-blocking phenotype in the Drosophila host. This provides additional evidence that the mechanistic basis of Wolbachia -mediated dengue virus blocking in insects is more complex than simple priming of the host insect innate immune system.

Natural variation at the Drosophila melanogaster Or22 odorant receptor locus is associated with changes in olfactory behaviour

Publisher: Cold Spring Harbor Laboratory

Date: 28-05-2021

DOI: 10.1101/2021.05.27.446061

Abstract: In insects many critical olfactory behaviours are mediated by the large odorant receptor (Or) gene family, which determine the response properties of different classes of olfactory receptor neurons (ORNs). While ORN responses are generally conserved within and between Drosophila species, variant alleles of the D.melanogaster Or22 locus have previously been shown to the response profiles of an ORN class called ab3A. These alleles show potential clinal variation, suggesting that selection is acting at this locus. Here, we investigated if the changes seen in ab3A responses lead to changes in olfactory-related behaviours. We show that variation at the Or22 locus and in the ab3A neurons are not fully compensated for by other ORNs and lead to overall changes in antennal odorant detection. We further show that this correlates with differences in odorant preference behaviour and with differences in oviposition site preference, with flies that have the chimaeric short allele strongly preferring to oviposit on banana. These findings indicate that variation at the Or22 locus leads to changes in olfactory-driven behaviours that could be under selective pressure, and add support to the idea that the ab3A neurons are of especial importance to the ecology of Drosophila flies.

Torso-like is a component of the hemolymph and regulates the insulin signaling pathway in drosophila

Publisher: Oxford University Press (OUP)

Date: 04-2018

DOI: 10.1534/GENETICS.117.300601

Abstract: In Drosophila, key developmental transitions are governed by the steroid hormone ecdysone. A number of neuropeptide-activated signaling pathways control ecdysone production in response to environmental signals, including the insulin signaling pathway, which regulates ecdysone production in response to nutrition. Here, we find that the Membrane Attack Complex/Perforin-like protein Torso-like, best characterized for its role in activating the Torso receptor tyrosine kinase in early embryo patterning, also regulates the insulin signaling pathway in Drosophila. We previously reported that the small body size and developmental delay phenotypes of torso-like null mutants resemble those observed when insulin signaling is reduced. Here we report that, in addition to growth defects, torso-like mutants also display metabolic and nutritional plasticity phenotypes characteristic of mutants with impaired insulin signaling. We further find that in the absence of torso-like, the expression of insulin-like peptides is increased, as is their accumulation in insulin-producing cells. Finally, we show that Torso-like is a component of the hemolymph and that it is required in the prothoracic gland to control developmental timing and body size. Taken together, our data suggest that the secretion of Torso-like from the prothoracic gland influences the activity of insulin signaling throughout the body in Drosophila.

Functional analysis of a Drosophila melanogaster olfactory receptor expressed in Sf9 cells

Publisher: Elsevier BV

Date: 2007

DOI: 10.1016/J.JNEUMETH.2006.07.005

Abstract: Olfactory receptors (ORs) are seven transmembrane proteins that are responsible for the transduction of volatiles into neuronal signals. Their low sequence homology means that the prediction of ligands for ORs based on extrapolation from empirical data of other ORs is difficult, so an experimental approach must be used. Here, we report a functional assay for insect ORs using calcium-imaging in Sf9 cells. We find that the interaction of the odorant, ethyl butyrate, with the Drosophila melanogaster olfactory receptor Or22a is both dose-dependent and highly sensitive, with Or22a responding to ethyl butyrate with an EC(50) of (1.58+/-0.82)x10(-11)M. This degree of sensitivity does not require the addition of odorant binding proteins or downstream signal transduction elements. Furthermore, we demonstrate that Or22a expressed in Sf9 cells has a similar response profile to a range of odorants previously tested in vivo. This functional assay system will provide a useful tool for the de-orphaning of ORs from a wide range of insect species that are yet to have ligands assigned, and will help provide insight into OR specificity and mechanism of activation.

Reduced glutathione biosynthesis in Drosophila melanogaster causes neuronal defects linked to copper deficiency

Publisher: Wiley

Date: 02-03-2016

DOI: 10.1111/JNC.13567

Abstract: Glutathione (GSH) is a tripeptide often considered to be the master antioxidant in cells. GSH plays an integral role in cellular redox regulation and is also known to have a role in mammalian copper homeostasis. In vitro evidence suggests that GSH is involved in copper uptake, sequestration and efflux. This study was undertaken to further investigate the roles that GSH plays in neuronal copper homeostasis in vivo, using the model organism Drosophila melanogaster. RNA interference-mediated knockdown of the Glutamate-cysteine ligase catalytic subunit gene (Gclc) that encodes the rate-limiting enzyme in GSH biosynthesis was utilised to genetically deplete GSH levels. When Gclc was knocked down in all neurons, this caused lethality, which was partially rescued by copper supplementation and was exacerbated by additional knockdown of the copper uptake transporter Ctr1A, or over-expression of the copper efflux transporter ATP7. Furthermore, when Gclc was knocked down in a subset of neuropeptide-producing cells, this resulted in adult progeny with unexpanded wings, a phenotype previously associated with copper dyshomeostasis. In these cells, Gclc suppression caused a decrease in axon branching, a phenotype further enhanced by ATP7 over-expression. Therefore, we conclude that GSH may play an important role in regulating neuronal copper levels and that reduction in GSH may lead to functional copper deficiency in neurons in vivo. We provide genetic evidence that glutathione (GSH) levels influence Cu content or distribution in vivo, in Drosophila neurons. GSH could be required for binding Cu imported by Ctr1A and distributing it to chaperones, such as Mtn, CCS and Atox1. Alternatively, GSH could modify the copper-binding and transport activities of Atox1 and the ATP7 efflux protein via glutathionylation of copper-binding cysteines.

Regulation of ecdysone production in Drosophila by neuropeptides and peptide hormones

Publisher: The Royal Society

Date: 02-2021

DOI: 10.1098/RSOB.200373

Abstract: In both mammals and insects, steroid hormones play a major role in directing the animal's progression through developmental stages. To maximize fitness outcomes, steroid hormone production is regulated by the environmental conditions experienced by the animal. In insects, the steroid hormone ecdysone mediates transitions between developmental stages and is regulated in response to environmental factors such as nutrition. These environmental signals are communicated to the ecdysone-producing gland via the action of neuropeptide and peptide hormone signalling pathways. While some of these pathways have been well characterized, there is evidence to suggest more signalling pathways than has previously been thought function to control ecdysone production, potentially in response to a greater range of environmental conditions. Here, we review the neuropeptide and peptide hormone signalling pathways known to regulate the production of ecdysone in the model genetic insect Drosophila melanogaster , as well as what is known regarding the environmental signals that trigger these pathways. Areas for future research are highlighted that can further contribute to our overall understanding of the complex orchestration of environmental, physiological and developmental cues that together produce a functioning adult organism.

Torso-like mediates extracellular accumulation of Furin-cleaved Trunk to pattern the Drosophila embryo termini

Publisher: Springer Science and Business Media LLC

Date: 28-10-2015

DOI: 10.1038/NCOMMS9759

Abstract: Patterning of the Drosophila embryonic termini is achieved by localized activation of the Torso receptor by the growth factor Trunk. Governing this event is the perforin-like protein Torso-like, which is localized to the extracellular space at the embryo poles and has long been proposed to control localized proteolytic activation of Trunk. However, a protease involved in terminal patterning remains to be identified, and the role of Torso-like remains unknown. Here we find that Trunk is cleaved intracellularly by Furin proteases. We further show that Trunk is secreted, and that levels of extracellular Trunk are greatly reduced in torso-like null mutants. On the basis of these and previous findings, we suggest that Torso-like functions to mediate secretion of Trunk, thus providing the mechanism for spatially restricted activation of Torso. Our data represent an alternative mechanism for the spatial control of receptor signalling, and define a different role for perforin-like proteins in eukaryotes.

Copper overload and deficiency both adversely affect the central nervous system of Drosophila

Publisher: Oxford University Press (OUP)

Date: 2014

DOI: 10.1039/C4MT00140K

Abstract: Ectopic neuronal copper efflux causes a functional copper deficiency leading to developmental lethality in Drosophila.

Systematic functional characterization of putative zinc transport genes and identification of zinc toxicosis phenotypes inDrosophila melanogaster

Publisher: The Company of Biologists

Date: 1

DOI: 10.1242/JEB.069260

Abstract: The heavy metal zinc is an essential component of the human diet and is incorporated as a structural component in up to 10% of all mammalian proteins. The physiological importance of zinc homeostasis at the cellular level and the molecular mechanisms involved in this process have become topics of increasing interest in recent years. We have performed a systematic functional characterization of the majority of the predicted Drosophila Zip (Zinc/iron regulated transporter-related protein) and ZnT genes, using the Gal4-UAS system to carry out both ubiquitous and targeted over expression and suppression studies for thirteen of the seventeen putative zinc transport genes identified to date. We find that six of these thirteen genes may be essential for fly viability and that three of the remaining seven demonstrate over expression phenotypes. Our findings reaffirm the previously proposed function of dZnT63C (CG17723: FBgn005432) as an important zinc efflux protein and indicate that the fly homolog of hZip1, dZip42C.1 (CG9428: FBgn0033096), is a strong zinc importer in Drosophila. By combining over expression of dZip42C.1 with suppression of dZnT63C we were able to produce easily identifiable zinc toxicosis phenotypes which can be rescued or worsened by modifying dietary zinc content. Our findings show that a genetically based zinc toxicosis situation can be therapeutically treated or exacerbated by modifications to the diet, providing a sensitized background for future, more detailed studies of Zip / ZNT function.

Integrating the Molecular and Cellular Basis of Odor Coding in the Drosophila Antenna

Publisher: Elsevier BV

Date: 03-2003

DOI: 10.1016/S0896-6273(03)00094-1

Abstract: We investigate how the molecular and cellular maps of the Drosophila olfactory system are integrated. A correspondence is established between in idual odor receptors, neurons, and odors. We describe the expression of the Or22a and Or22b receptor genes, show localization to dendritic membranes, and find sexual dimorphism. Or22a maps to the ab3A neuron, which responds to ethyl butyrate. Analysis of a deletion mutant lacking Or22a, along with transgenic rescue experiments, confirms the mapping and demonstrates that an Or gene is required for olfactory function in vivo. Ectopic expression of Or47a in a mutant cell identifies the neuron from which it derives and its odor ligands. Ectopic expression in a wild-type cell shows that two receptors can function in a single cell. The ab3A neuron does not depend on normal odor receptor gene expression to navigate to its target in the CNS.

Using Mouse and Drosophila Models to Investigate the Mechanistic Links between Diet, Obesity, Type II Diabetes, and Cancer

Publisher: MDPI AG

Date: 18-12-2018

DOI: 10.3390/IJMS19124110

Abstract: Many of the links between diet and cancer are controversial and over simplified. To date, human epidemiological studies consistently reveal that patients who suffer diet-related obesity and/or type II diabetes have an increased risk of cancer, suffer more aggressive cancers, and respond poorly to current therapies. However, the underlying molecular mechanisms that increase cancer risk and decrease the response to cancer therapies in these patients remain largely unknown. Here, we review studies in mouse cancer models in which either dietary or genetic manipulation has been used to model obesity and/or type II diabetes. These studies demonstrate an emerging role for the conserved insulin and insulin-like growth factor signaling pathways as links between diet and cancer progression. However, these models are time consuming to develop and expensive to maintain. As the world faces an epidemic of obesity and type II diabetes we argue that the development of novel animal models is urgently required. We make the case for Drosophila as providing an unparalleled opportunity to combine dietary manipulation with models of human metabolic disease and cancer. Thus, combining diet and cancer models in Drosophila can rapidly and significantly advance our understanding of the conserved molecular mechanisms that link diet and diet-related metabolic disorders to poor cancer patient prognosis.

Selective Pressures on Drosophila Chemosensory Receptor Genes

Publisher: Springer Science and Business Media LLC

Date: 29-05-2007

DOI: 10.1007/S00239-006-0151-6

Abstract: The evolution and patterns of selection of genes encoding 10 Drosophila odorant receptors (Or) and the sex pheromone receptor Gr68a were investigated by comparing orthologous sequences across five to eight ecologically erse species of Drosophila. Using maximum likelihood estimates of dN/dS ratios we show that all 11 genes s led are under purifying selection, indicating functional constraint. Four of these genes (Or33c, Or42a, Or85e, and Gr68a) may be under positive selection, and if so, there is good evidence that 12 specific amino acid sites may be under positive selection. All of these sites are predicted to be located either in loop regions or just inside membrane spanning regions, and interestingly one of the two sites in Gr68a is in a similar position to a previously described polymorphism in Gr5a that causes a shift in sensitivity to its ligand trehalose. For three Ors, possible evidence for positive selection was detected along a lineage. These include Or22a in the lineage leading to D. mauritiana and Or22b in the lineage leading to D. simulans. This is of interest in light of previous data showing a change in ligand response profile for these species in the sensory neuron (ab3A) which expresses both Or22a and Or22b in D. melanogaster. In summary, while the main chemosensory function and/or structural integrity of these 10 Or genes and Gr68a are evolutionarily preserved, positive selection appears to be acting on some of these genes, at specific sites and along certain lineages, and provides testable hypotheses for further functional experimentation.

Vacuolar-type H⁺-ATPase subunits and the neurogenic protein big brain are required for optimal copper and zinc uptake

Publisher: Oxford University Press (OUP)

Date: 2014

DOI: 10.1039/C4MT00196F

Abstract: Disruption of possible endocytic recycling pathways disturbs cellular copper and zinc accumulation in Drosophila .

Differential regulation of protein tyrosine kinase signalling by Dock and the PTP61F variants

Publisher: Wiley

Date: 30-06-2017

DOI: 10.1111/FEBS.14118

Abstract: Tyrosine phosphorylation-dependent signalling is coordinated by the opposing actions of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). There is a growing list of adaptor proteins that interact with PTPs and facilitate the dephosphorylation of substrates. The extent to which any given adaptor confers selectivity for any given substrate in vivo remains unclear. Here we have taken advantage of Drosophila melanogaster as a model organism to explore the influence of the SH3/SH2 adaptor protein Dock on the abilities of the membrane (PTP61Fm)- and nuclear (PTP61Fn)-targeted variants of PTP61F (the Drosophila othologue of the mammalian enzymes PTP1B and TCPTP respectively) to repress PTK signalling pathways in vivo. PTP61Fn effectively repressed the eye overgrowth associated with activation of the epidermal growth factor receptor (EGFR), PTK, or the expression of the platelet-derived growth factor/vascular endothelial growth factor receptor (PVR) or insulin receptor (InR) PTKs. PTP61Fn repressed EGFR and PVR-induced mitogen-activated protein kinase signalling and attenuated PVR-induced STAT92E signalling. By contrast, PTP61Fm effectively repressed EGFR- and PVR-, but not InR-induced tissue overgrowth. Importantly, coexpression of Dock with PTP61F allowed for the efficient repression of the InR-induced eye overgrowth, but did not enhance the PTP61Fm-mediated inhibition of EGFR and PVR-induced signalling. Instead, Dock expression increased, and PTP61Fm coexpression further exacerbated the PVR-induced eye overgrowth. These results demonstrate that Dock selectively enhances the PTP61Fm-mediated attenuation of InR signalling and underscores the specificity of PTPs and the importance of adaptor proteins in regulating PTP function in vivo.

Olfaction in Drosophila: Coding, Genetics and e-Genetics

Publisher: Oxford University Press (OUP)

Date: 02-2001

DOI: 10.1093/CHEMSE/26.2.201

Abstract: Odor coding in Drosophila is examined at both the cellular and molecular levels. Functional analysis of in idual olfactory receptor neurons (ORNs) by single-unit electrophysiology has shown that ORNs ide into discrete classes, with each class exhibiting a characteristic odor response spectrum. Extensive analysis of ORNs in the maxillary palp has revealed six such classes, which are combined in sensilla according to a strict pairing rule. In order to identify the odor receptor genes that determine the odor specificity of these ORN classes, a new algorithm was designed to search DNA databases for proteins with a particular structure, as opposed to a particular sequence. The algorithm identified a large family of genes likely to encode odor receptors. The acj6 gene, originally identified in a screen for mutants defective in olfactory behavior, encodes a transcription factor that regulates a subset of these receptor genes, and is likely to play a critical role in the process by which ORNs select which receptors to express.

Candidate Taste Receptors in Drosophila

Publisher: American Association for the Advancement of Science (AAAS)

Date: 10-03-2000

DOI: 10.1126/SCIENCE.287.5459.1830

Abstract: Little is known about the molecular mechanisms of taste perception in animals, particularly the initial events of taste signaling. A large and erse family of seven transmembrane domain proteins was identified from the Drosophila genome database with a computer algorithm that identifies proteins on the basis of structure. Eighteen of 19 genes examined were expressed in the Drosophila labellum, a gustatory organ of the proboscis. Expression was not detected in a variety of other tissues. The genes were not expressed in the labellum of a Drosophila mutant, pox-neuro 70 , in which taste neurons are eliminated. Tissue specificity of expression of these genes, along with their structural similarity, supports the possibility that the family encodes a large and ergent family of taste receptors.

Identification and characterization of two distinct calmodulin-binding sites in the Trpl ion-channel protein of Drosophila melanogaster

Publisher: Portland Press Ltd.

Date: 03-1996

DOI: 10.1042/BJ3140497

Abstract: Two putative light-sensitive ion channels have been isolated from Drosophila, encoded by the transient-receptor-potential (trp) and transient-receptor-potential-like (trpl) genes. The cDNA encoding the Trpl protein was initially isolated on the basis that the expressed protein binds calmodulin. Using both fusion proteins and a synthetic peptide, we now show that two calmodulin-binding sites are present in the C-terminal domain of the Trpl protein, CBS-1 and CBS-2. CBS-1 binds calmodulin in a Ca2+-dependent fashion, requiring Ca2+ concentrations above 0.3–0.5 μM for calmodulin binding. In contrast, CBS-2 binds the Ca2+-free form of calmodulin, with dissociation occurring at Ca2+ concentrations between 5 and 25 μM. Phosphorylation of a serine residue within a peptide encompassing CBS-1 by cyclic AMP-dependent protein kinase (PKA) abolishes calmodulin binding, and phosphorylation of the adjacent serine by protein kinase C appears to modulate this phosphorylation by PKA. Interpretation of these findings provides a novel model for ion-channel gating and modulation in response to changing levels of intracellular Ca2+.

Two uptake hydrogenases differentially interact with the aerobic respiratory chain during mycobacterial growth and persistence

Publisher: Elsevier BV

Date: 12-2019

DOI: 10.1074/JBC.RA119.011076

Chemical Communication in Insects: The Peripheral Odour Coding System of Drosophila Melanogaster

Publisher: Springer US

Date: 2012

DOI: 10.1007/978-1-4614-1704-0_4

Abstract: Animals use their chemosensory systems to detect and discriminate among chemical cues in the environment. Remarkable progress has recently been made in our knowledge of the molecular and cellular basis of chemosensory perception in insects, based largely on studies in the vinegar fly Drosophila melanogaster. This progress has been possible due to the identification of gene families for olfactory receptors, the use of electro-physiological recording techniques on sensory neurons, the manifold of genetic manipulations that are available in this species and insights from several insect model systems. The superfamilies of olfactory receptor proteins, the Or genes and the more recently discovered IR genes, represent the essential elements in olfactory coding, endowing olfactory receptor neurons with their abilities to respond to specific sets of odorants or pheromones. General odorants activate receptors in a combinatorial fashion, but some receptors are narrowly tuned to pheromones or to carbon dioxide. Surprisingly, olfactory receptors in insects are biochemically quite different to those in mammals and do not appear to signal via classical G protein pathways but rather via ionotropic mechanisms. Here we review the past decade of intensive research since the discovery of the first insect olfactory receptors in 1999, focusing on the molecules and cells that underly peripheral olfactory perception in Drosophila.

Therapeutic Potential of Tea Tree Oil for Scabies

Publisher: American Society of Tropical Medicine and Hygiene

Date: 03-02-2016

DOI: 10.4269/AJTMH.14-0515

A Syndromic Neurodevelopmental Disorder Caused by De Novo Variants in EBF3

Publisher: Elsevier BV

Date: 2017

DOI: 10.1016/J.AJHG.2016.11.018

The nucleus- and endoplasmic reticulum-targeted forms of protein tyrosine phosphatase 61F regulate Drosophila growth, life span, and fecundity.

Publisher: Informa UK Limited

Date: 04-2013

DOI: 10.1128/MCB.01411-12

MACPF/CDC proteins in development: Insights from Drosophila torso-like

Publisher: Elsevier BV

Date: 12-2017

DOI: 10.1016/J.SEMCDB.2017.05.003

Abstract: The Membrane Attack Complex Perforin-like/Cholesterol-Dependent Cytolysin (MACPF) superfamily is an ancient and biologically erse group of proteins that are best known for pore-forming roles in mammalian immunity and bacterial pathogenesis. Intriguingly, however, some eukaryotic proteins which contain the MACPF domain that defines this family do not act in attack or defence, and instead have distinct developmental functions. It remains unclear whether these proteins function via pore formation or have a different mechanism of action. Of these, by far the best characterised is Torso-like (Tsl), the only MACPF member that has been identified in the fruit fly, Drosophila melanogaster. While it has long been known to have a role in embryonic patterning, recent studies have shown that Tsl in fact has multiple roles in development. As such, it presents an excellent opportunity to investigate how the MACPF domain functions in a developmental context. Here, we review what is known about Tsl in Drosophila and other insects, and discuss the potential molecular mechanism by which Tsl and thus other developmental MACPF proteins may function.

Drosophila olfactory receptors as classifiers for volatiles from disparate real world applications

Publisher: IOP Publishing

Date: 14-10-2014

DOI: 10.1088/1748-3182/9/4/046007

Abstract: Olfactory receptors evolved to provide animals with ecologically and behaviourally relevant information. The resulting extreme sensitivity and discrimination has proven useful to humans, who have therefore co-opted some animals' sense of smell. One aim of machine olfaction research is to replace the use of animal noses and one avenue of such research aims to incorporate olfactory receptors into artificial noses. Here, we investigate how well the olfactory receptors of the fruit fly, Drosophila melanogaster, perform in classifying volatile odourants that they would not normally encounter. We collected a large number of in vivo recordings from in idual Drosophila olfactory receptor neurons in response to an ecologically relevant set of 36 chemicals related to wine ('wine set') and an ecologically irrelevant set of 35 chemicals related to chemical hazards ('industrial set'), each chemical at a single concentration. Res led response sets were used to classify the chemicals against all others within each set, using a standard linear support vector machine classifier and a wrapper approach. Drosophila receptors appear highly capable of distinguishing chemicals that they have not evolved to process. In contrast to previous work with metal oxide sensors, Drosophila receptors achieved the best recognition accuracy if the outputs of all 20 receptor types were used.

Development of the Cellular Immune System of Drosophila Requires the Membrane Attack Complex/Perforin-Like Protein Torso-Like.

Publisher: Oxford University Press (OUP)

Date: 10-2016

DOI: 10.1534/GENETICS.115.185462

Abstract: Pore-forming members of the membrane attack complex erforin-like (MACPF) protein superfamily perform well-characterized roles as mammalian immune effectors. For ex le, complement component 9 and perforin function to directly form pores in the membrane of Gram-negative pathogens or virally infected/transformed cells, respectively. In contrast, the only known MACPF protein in Drosophila melanogaster, Torso-like, plays crucial roles during development in embryo patterning and larval growth. Here, we report that in addition to these functions, Torso-like plays an important role in Drosophila immunity. However, in contrast to a hypothesized effector function in, for ex le, elimination of Gram-negative pathogens, we find that torso-like null mutants instead show increased susceptibility to certain Gram-positive pathogens such as Staphylococcus aureus and Enterococcus faecalis. We further show that this deficit is due to a severely reduced number of circulating immune cells and, as a consequence, an impaired ability to phagocytose bacterial particles. Together these data suggest that Torso-like plays an important role in controlling the development of the Drosophila cellular immune system.

A role for dZIP89B in Drosophila dietary zinc uptake reveals additional complexity in the zinc absorption process

Publisher: Elsevier BV

Date: 12-2015

DOI: 10.1016/J.BIOCEL.2015.10.004

Abstract: Dietary zinc is the principal source of zinc in eukaryotes, with its uptake and distribution controlled by a complex network of numerous membrane-spanning transport proteins. Dietary absorption is achieved by members of the SLC39A (ZIP) gene family, which encode proteins that are generally responsible for the movement of zinc into the cytosol. ZIP4 is thought to be the primary mammalian zinc uptake gene in the small intestine, with mutations in this gene causing the zinc deficiency disease Acrodermatitis enteropathica. In Drosophila, dual knockdown of the major dietary zinc uptake genes dZIP42C.1 (dZIP1) and dZIP42C.2 (dZIP2) results in a severe sensitivity to zinc-deficient media. However, the symptoms associated with ZIP4 loss can be reversed by zinc supplementation and dZIP42C.1 and 2 knockdown has minimal effect under normal dietary conditions, suggesting that additional pathways for zinc absorption exist in both mammals and flies. This study provides evidence that dZIP89B is an ideal candidate for this role in Drosophila, encoding a low-affinity zinc uptake transporter active in the posterior midgut. Flies lacking dZIP89B, while viable and apparently healthy, show indications of low midgut zinc levels, including reduced metallothionein B expression and compensatory up-regulation of dZIP42C.1 and 2. Furthermore dZIP89B mutants display a dramatic resistance to toxic dietary zinc levels which is abrogated by midgut-specific restoration of dZIP89B activity. We postulate that dZIP89B works in concert with the closely related dZIP42C.1 and 2 to ensure optimal zinc absorption under a range of dietary conditions.

Molecular and cellular organization of insect chemosensory neurons

Publisher: Wiley

Date: 2005

DOI: 10.1002/BIES.20338

Abstract: Animals use their chemosensory systems to detect and discriminate among chemical cues in the environment. Remarkable progress has recently been made in our knowledge of the molecular and cellular basis of chemosensory perception in insects, based largely on studies in Drosophila. This progress has been possible due to the identification of gene families for olfactory and gustatory receptors, the use of electro-physiological recording techniques on sensory neurons, the multitude of genetic manipulations that are available in this species, and insights from several insect model systems. Recent studies show that the superfamily of chemoreceptor proteins represent the essential elements in chemosensory coding, endowing chemosensory neurons with their abilities to respond to specific sets of odorants, tastants or pheromones. Investigating how insects detect chemicals in their environment can show us how receptor protein structures relate to ligand binding, how nervous systems process complex information, and how chemosensory systems and genes evolve.

Maternal Torso-Like Coordinates Tissue Folding During Drosophila Gastrulation

Publisher: Oxford University Press (OUP)

Date: 07-2017

DOI: 10.1534/GENETICS.117.200576

Abstract: The rapid and orderly folding of epithelial tissue during developmental processes such as gastrulation requires the precise coordination of changes in cell shape. Here, we report that the perforin-like protein Torso-like (Tsl), the key extracellular determinant for Drosophila embryonic terminal patterning, also functions to control epithelial morphogenesis. We find that tsl null mutants display a ventral cuticular hole phenotype that is independent of the loss of terminal structures, and arises as a consequence of mesoderm invagination defects. We show that the holes are caused by uncoordinated constriction of ventral cell apices, resulting in the formation of an incomplete ventral furrow. Consistent with these data, we find that loss of tsl is sensitive to gene dosage of RhoGEF2, a critical mediator of Rho1-dependent ventral cell shape changes during furrow formation, suggesting that Tsl may act in this pathway. In addition, loss of tsl strongly suppressed the effects of ectopic expression of Folded Gastrulation (Fog), a secreted protein that promotes apical constriction. Taken together, our data suggest that Tsl controls Rho1-mediated apical constriction via Fog. Therefore, we propose that Tsl regulates extracellular Fog activity to synchronize cell shape changes and coordinate ventral morphogenesis in Drosophila. Identifying the Tsl-mediated event that is common to both terminal patterning and morphogenesis will be valuable for our understanding of the extracellular control of developmental signaling by perforin-like proteins.

A Screen for Genes Expressed in the Olfactory Organs of Drosophila melanogaster Identifies Genes Involved in Olfactory Behaviour

Publisher: Public Library of Science (PLoS)

Date: 18-04-2012

DOI: 10.1371/JOURNAL.PONE.0035641

Molecular and Functional Evolution at the Odorant Receptor Or22 Locus in Drosophila melanogaster.

Publisher: Oxford University Press (OUP)

Date: 15-02-2019

DOI: 10.1093/MOLBEV/MSZ018

Drosophila odorant receptors are novel seven transmembrane domain proteins that can signal independently of heterotrimeric G proteins

Publisher: Elsevier BV

Date: 08-2008

DOI: 10.1016/J.IBMB.2008.05.002

Abstract: Olfaction in Drosophila is mediated by a large family of membrane-bound odorant receptor proteins (Ors). In heterologous cells, we investigated whether the structural features and signalling mechanisms of ligand-binding Drosophila Ors are consistent with them being G protein-coupled receptors (GPCRs). The detailed membrane topology of Or22a was determined by inserting epitope tags into the termini and predicted loop regions. Immunocytochemistry experiments in Drosophila S2 cells imply that Or22a has seven transmembrane domains but that its membrane topology is opposite to that of GPCRs, with a cytoplasmic N-terminus and extracellular C-terminus. To investigate Or signalling mechanisms, we expressed Or43b in Sf9 and HEK293 cells, and show that inhibitors of heterotrimeric G proteins (GDP-beta-S), adenylate cyclase (SQ22536), guanylyl cyclase (ODQ), cyclic nucleotide phosphodiesterases (IBMX) and phospholipase C (U73122) have negligible impact on Or43b responses. Whole cell patching of Or43b/Or83b-transfected HEK293 cells revealed the opening of plasma membrane cation channels on addition of ligand. The response was blocked by lanthanum and by 2-APB, but not by Ruthenium red or SKF96365. Based on these data, we conclude that Drosophila Ors comprise a novel family of seven transmembrane receptors that in HEK293 cells signal by opening cation channels, through a mechanism that is largely independent of G proteins.

Identification of novel multi-transmembrane proteins from genomic databases using quasi-periodic structural properties

Publisher: Oxford University Press (OUP)

Date: 09-2000

DOI: 10.1093/BIOINFORMATICS/16.9.767

Abstract: Motivation: Identification of novel G protein-coupled receptors and other multi-transmembrane proteins from genomic databases using structural features. Results: Here we describe a new algorithm for identifying multi-transmembrane proteins from genomic databases with a specific application to identifying G protein-coupled receptors (GPCRs) that we call quasi-periodic feature classifier (QFC). The QFC algorithm uses concise statistical variables as the ‘feature space’ to characterize the quasi-periodic physico-chemical properties of multi-transmembrane proteins. For the case of identifying GPCRs, the variables are then used in a non-parametric linear discriminant function to separate GPCRs from non-GPCRs. The algorithm runs in time linearly proportional to the number of sequences, and performance on a test dataset shows 96% positive identification of known GPCRs. The QFC algorithm also works well with short random segments of proteins and it positively identified GPCRs at a level greater than 90% even with segments as short as 100 amino acids. The primary advantage of the algorithm is that it does not directly use primary sequence patterns which may be subject to s ling bias. The utility of the new algorithm has been demonstrated by the isolation from the Drosophila genome project database of a novel class of seven-transmembrane proteins which were shown to be the elusive olfactory receptor genes of Drosophila. Availability: C++/Perl available from ndex.html Contact: Junhyong Kim, Dept. of Ecology and Evolutionary Biology, Yale University, P.O. Box 208106, New Haven, CT 06520-8106 junhyong.kim@yale.edu Supplementary information: Test dataset and training dataset are available from ndex.html **** To whom correspondence should be addressed.

Torso-like functions independently of Torso to regulate Drosophila growth and developmental timing.

Publisher: Proceedings of the National Academy of Sciences

Date: 19-08-2013

DOI: 10.1073/PNAS.1309780110

Abstract: Torso-like (Tsl) is the sole Drosophila member of the membrane attack complex erforin-like protein superfamily, generally known for pore-forming function and immune defence roles. Tsl, however, has a well-characterized developmental role in controlling activation of the receptor tyrosine kinase Torso (Tor) to achieve patterning of the termini of the early embryo. Here we report that the second known role of Tor, as the receptor for the hormone that induces metamorphosis, does not require Tsl. Instead, we find that Tsl controls developmental timing and growth independently of Tor. We conclude that Tsl plays a broader than expected role during development and is not merely a specialized cue for Tor signaling.

Coexpression of Two Functional Odor Receptors in One Neuron

Publisher: Elsevier BV

Date: 03-2005

DOI: 10.1016/J.NEURON.2005.01.025

Abstract: One of the most fundamental tenets in the field of olfaction is that each olfactory receptor neuron (ORN) expresses a single odorant receptor. However, the one receptor-one neuron principle is difficult to establish rigorously. Here we construct a receptor-to-neuron map for an entire olfactory organ in Drosophila and find that two receptor genes are coexpressed in one class of ORN. Both receptors are functional in an in vivo expression system, they are only 16% identical in amino acid sequence, and the genes that encode them are unlinked. Most importantly, their coexpression has been conserved for >45 million years. Expression of multiple odor receptors in a cell provides an additional degree of freedom for odor coding.

Monash University

Location: Australia

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La Trobe University

Location: Australia

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University Of Melbourne

Location: Australia

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University Of Tasmania

Location: Australia

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Discovery Projects - Grant ID: DP0210435

Start Date: 2002

End Date: 06-2005

Amount: $141,000.00

Funder: Australian Research Council

Discovery Projects - Grant ID: DP0559370

Start Date: 2005

End Date: 12-2008

Amount: $255,000.00

Funder: Australian Research Council

Discovery Projects - Grant ID: DP140102771

Start Date: 2014

End Date: 12-2016

Amount: $540,000.00

Funder: Australian Research Council

Discovery Projects - Grant ID: DP110100622

Start Date: 2011

End Date: 02-2015

Amount: $390,000.00

Funder: Australian Research Council

Discovery Projects - Grant ID: DP160102797

Start Date: 2016

End Date: 06-2021

Amount: $379,400.00

Funder: Australian Research Council

Discovery Projects - Grant ID: DP200101635

Start Date: 02-2020

End Date: 12-2023

Amount: $578,043.00

Funder: Australian Research Council

Special Research Initiatives - Grant ID: SR0354908

Start Date: 2004

End Date: 12-2004

Amount: $10,000.00

Funder: Australian Research Council