@article {163, title = {Genes involved in sex pheromone discrimination in Drosophila melanogaster and their background-dependent effect.}, journal = {PLoS One}, volume = {7}, year = {2012}, month = {2012}, pages = {e30799}, abstract = {

Mate choice is based on the comparison of the sensory quality of potential mating partners, and sex pheromones play an important role in this process. In Drosophila melanogaster, contact pheromones differ between male and female in their content and in their effects on male courtship, both inhibitory and stimulatory. To investigate the genetic basis of sex pheromone discrimination, we experimentally selected males showing either a higher or lower ability to discriminate sex pheromones over 20 generations. This experimental selection was carried out in parallel on two different genetic backgrounds: wild-type and desat1 mutant, in which parental males showed high and low sex pheromone discrimination ability respectively. Male perception of male and female pheromones was separately affected during the process of selection. A comparison of transcriptomic activity between high and low discrimination lines revealed genes not only that varied according to the starting genetic background, but varied reciprocally. Mutants in two of these genes, Shaker and quick-to-court, were capable of producing similar effects on discrimination on their own, in some instances mimicking the selected lines, in others not. This suggests that discrimination of sex pheromones depends on genes whose activity is sensitive to genetic context and provides a rare, genetically defined example of the phenomenon known as "allele flips," in which interactions have reciprocal effects on different genetic backgrounds.

}, keywords = {Animals, Animals, Genetically Modified, Behavior, Animal, Breeding, Courtship, Drosophila melanogaster, Female, Genes, Insect, Male, Mutation, Olfactory Perception, Reproduction, Sex Attractants, Sexual Behavior, Animal, Species Specificity}, issn = {1932-6203}, doi = {10.1371/journal.pone.0030799}, author = {Houot, Benjamin and Fraichard, St{\'e}phane and Greenspan, Ralph J and Ferveur, Jean-Fran{\c c}ois} } @article {165, title = {The Drosophila foraging gene mediates adult plasticity and gene-environment interactions in behaviour, metabolites, and gene expression in response to food deprivation.}, journal = {PLoS Genet}, volume = {5}, year = {2009}, month = {2009 Aug}, pages = {e1000609}, abstract = {

Nutrition is known to interact with genotype in human metabolic syndromes, obesity, and diabetes, and also in Drosophila metabolism. Plasticity in metabolic responses, such as changes in body fat or blood sugar in response to changes in dietary alterations, may also be affected by genotype. Here we show that variants of the foraging (for) gene in Drosophila melanogaster affect the response to food deprivation in a large suite of adult phenotypes by measuring gene by environment interactions (GEI) in a suite of food-related traits. for affects body fat, carbohydrates, food-leaving behavior, metabolite, and gene expression levels in response to food deprivation. This results in broad patterns of metabolic, genomic, and behavioral gene by environment interactions (GEI), in part by interaction with the insulin signaling pathway. Our results show that a single gene that varies in nature can have far reaching effects on behavior and metabolism by acting through multiple other genes and pathways.

}, keywords = {Animals, Carbohydrate Metabolism, Cyclic GMP-Dependent Protein Kinases, Drosophila melanogaster, Drosophila Proteins, Ecosystem, Fats, Food Deprivation, Gene Expression, Signal Transduction}, issn = {1553-7404}, doi = {10.1371/journal.pgen.1000609}, author = {Kent, Clement F and Daskalchuk, Tim and Cook, Lisa and Sokolowski, Marla B and Greenspan, Ralph J} } @article {142, title = {Selection, gene interaction, and flexible gene networks.}, journal = {Cold Spring Harb Symp Quant Biol}, volume = {74}, year = {2009}, month = {2009}, pages = {131-8}, abstract = {

Recent results from a variety of different kinds of experiments, mainly using behavior as an assay, and ranging from laboratory selection experiments to gene interaction studies, show that a much wider range of genes can affect phenotype than those identified as "core genes" in classical mutant screens. Moreover, very pleiotropic genes can produce specific phenotypes when mild variants are combined. These studies also show that gene networks readily change configuration and the relationships between interacting genes in response to the introduction of additional genetic variants, suggesting that the networks range widely and have a high degree of flexibility and malleability. Such flexibility, in turn, offers a plausible mechanism for the molding of phenotypes through microevolution, as a prerequisite to making a suitable environment for the acceptance of newly arising large-effect mutations in the transition from microevolution to macroevolution.

}, keywords = {Animals, Biological Evolution, Drosophila melanogaster, Epistasis, Genetic, Escherichia coli, Female, Gene Regulatory Networks, Genes, Insect, Genetic Association Studies, Male, Models, Genetic, Mutation, Selection, Genetic}, issn = {1943-4456}, doi = {10.1101/sqb.2009.74.029}, author = {Greenspan, R J} } @article {144, title = {Serotonin and neuropeptide F have opposite modulatory effects on fly aggression.}, journal = {Nat Genet}, volume = {39}, year = {2007}, month = {2007 May}, pages = {678-82}, abstract = {

Both serotonin (5-HT) and neuropeptide Y have been shown to affect a variety of mammalian behaviors, including aggression. Here we show in Drosophila melanogaster that both 5-HT and neuropeptide F, the invertebrate homolog of neuropeptide Y, modulate aggression. We show that drug-induced increases of 5-HT in the fly brain increase aggression. Elevating 5-HT genetically in the serotonergic circuits recapitulates these pharmacological effects, whereas genetic silencing of these circuits makes the flies behaviorally unresponsive to the drug-induced increase of 5-HT but leaves them capable of aggression. Genetic silencing of the neuropeptide F (npf) circuit also increases fly aggression, demonstrating an opposite modulation to 5-HT. Moreover, this neuropeptide F effect seems to be independent of 5-HT. The implication of these two modulatory systems in fly and mouse aggression suggest a marked degree of conservation and a deep molecular root for this behavior.

}, keywords = {Aggression, Analysis of Variance, Animals, Behavior, Animal, Biological Evolution, Brain, Drosophila melanogaster, Drosophila Proteins, Gene Silencing, Neuropeptides, Reverse Transcriptase Polymerase Chain Reaction, Serotonin}, issn = {1061-4036}, doi = {10.1038/ng2029}, author = {Dierick, Herman A and Greenspan, Ralph J} } @article {145, title = {Molecular analysis of flies selected for aggressive behavior.}, journal = {Nat Genet}, volume = {38}, year = {2006}, month = {2006 Sep}, pages = {1023-31}, abstract = {

Aggressive behavior is pervasive throughout the animal kingdom, and yet very little is known about its molecular underpinnings. To address this problem, we have developed a population-based selection procedure to increase aggression in Drosophila melanogaster. We measured changes in aggressive behavior in the selected subpopulations with a new two-male arena assay. In only ten generations of selection, the aggressive lines became markedly more aggressive than the neutral lines. After 21 generations, the fighting index increased more than 30-fold. Using microarray analysis, we identified genes with differing expression levels in the aggressive and neutral lines as candidates for this strong behavioral selection response. We tested a small set of these genes through mutant analysis and found that one significantly increased fighting frequency. These results suggest that selection for increases in aggression can be used to molecularly dissect this behavior.

}, keywords = {Aggression, Agonistic Behavior, Animals, Behavior, Animal, DNA Mutational Analysis, Drosophila melanogaster, Male, Oligonucleotide Array Sequence Analysis, RNA, Selection, Genetic}, issn = {1061-4036}, doi = {10.1038/ng1864}, author = {Dierick, Herman A and Greenspan, Ralph J} } @article {148, title = {Cognitive consonance: complex brain functions in the fruit fly and its relatives.}, journal = {Trends Neurosci}, volume = {27}, year = {2004}, month = {2004 Dec}, pages = {707-11}, abstract = {

The fruit fly, Drosophila melanogaster, has become a model for the study of a growing number of human characteristics because of the power of its genetics. Higher cognitive functions, however, might be assumed to be out of reach for the little fly. But the cumulative history of cognitive studies in insects and some of their arachnid relatives, as well as specific probing of the capabilities of fruit flies, suggests that even in this ethereal realm these creatures have much to contribute. What are the degrees of sophistication in cognitive behavior displayed by these organisms, how have they been demonstrated, and what is their potential for understanding how our own brains work?

}, keywords = {Animals, Bees, Behavior, Animal, Brain, Cognition, Drosophila melanogaster, Humans, Perception, Spiders}, issn = {0166-2236}, doi = {10.1016/j.tins.2004.10.002}, author = {Greenspan, Ralph J and van Swinderen, Bruno} } @article {150, title = {Identification of genes involved in Drosophila melanogaster geotaxis, a complex behavioral trait.}, journal = {Nat Genet}, volume = {31}, year = {2002}, month = {2002 Aug}, pages = {349-53}, abstract = {

Identifying the genes involved in polygenic traits has been difficult. In the 1950s and 1960s, laboratory selection experiments for extreme geotaxic behavior in fruit flies established for the first time that a complex behavioral trait has a genetic basis. But the specific genes responsible for the behavior have never been identified using this classical model. To identify the individual genes involved in geotaxic response, we used cDNA microarrays to identify candidate genes and assessed fly lines mutant in these genes for behavioral confirmation. We have thus determined the identities of several genes that contribute to the complex, polygenic behavior of geotaxis.

}, keywords = {Animals, Animals, Genetically Modified, Behavior, Animal, DNA, Complementary, Drosophila melanogaster, Female, Genetics, Behavioral, Mutation, Oligonucleotide Array Sequence Analysis}, issn = {1061-4036}, doi = {10.1038/ng893}, author = {Toma, Daniel P and White, Kevin P and Hirsch, Jerry and Greenspan, Ralph J} } @article {152, title = {Correlates of sleep and waking in Drosophila melanogaster.}, journal = {Science}, volume = {287}, year = {2000}, month = {2000 Mar 10}, pages = {1834-7}, abstract = {

Drosophila exhibits a circadian rest-activity cycle, but it is not known whether fly rest constitutes sleep or is mere inactivity. It is shown here that, like mammalian sleep, rest in Drosophila is characterized by an increased arousal threshold and is homeostatically regulated independently of the circadian clock. As in mammals, rest is abundant in young flies, is reduced in older flies, and is modulated by stimulants and hypnotics. Several molecular markers modulated by sleep and waking in mammals are modulated by rest and activity in Drosophila, including cytochrome oxidase C, the endoplasmic reticulum chaperone protein BiP, and enzymes implicated in the catabolism of monoamines. Flies lacking one such enzyme, arylalkylamine N-acetyltransferase, show increased rest after rest deprivation. These results implicate the catabolism of monoamines in the regulation of sleep and waking in the fly and suggest that Drosophila may serve as a model system for the genetic dissection of sleep.

}, keywords = {Animals, Arylamine N-Acetyltransferase, Behavior, Animal, Biogenic Monoamines, Caffeine, Carrier Proteins, Circadian Rhythm, Cytochrome P-450 Enzyme System, Drosophila melanogaster, Drosophila Proteins, Fatty Acid Synthases, Female, Gene Dosage, Gene Expression Profiling, Genes, Insect, Homeostasis, HSC70 Heat-Shock Proteins, HSP70 Heat-Shock Proteins, Hydroxyzine, Mutation, Rest, Sleep, Transcription, Genetic, Wakefulness}, issn = {0036-8075}, author = {Shaw, P J and Cirelli, C and Greenspan, R J and Tononi, G} } @article {153, title = {Natural behavior polymorphism due to a cGMP-dependent protein kinase of Drosophila.}, journal = {Science}, volume = {277}, year = {1997}, month = {1997 Aug 8}, pages = {834-6}, abstract = {

Naturally occuring polymorphisms in behavior are difficult to map genetically and thus are refractory to molecular characterization. An exception is the foraging gene (for), a gene that has two naturally occurring variants in Drosophila melanogaster food-search behavior: rover and sitter. Molecular mapping placed for mutations in the dg2 gene, which encodes a cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG). Rovers had higher PKG activity than sitters, and transgenic sitters expressing a dg2 complementary DNA from rover showed transformation of behavior to rover. Thus, PKG levels affected food-search behavior, and natural variation in PKG activity accounted for a behavioral polymorphism.

}, keywords = {Animals, Animals, Genetically Modified, Cyclic GMP, Cyclic GMP-Dependent Protein Kinases, Drosophila melanogaster, Feeding Behavior, Genes, Insect, Larva, Phenotype, Polymorphism, Genetic, Signal Transduction}, issn = {0036-8075}, author = {Osborne, K A and Robichon, A and Burgess, E and Butland, S and Shaw, R A and Coulthard, A and Pereira, H S and Greenspan, R J and Sokolowski, M B} } @article {154, title = {Genetic feminization of brain structures and changed sexual orientation in male Drosophila.}, journal = {Science}, volume = {267}, year = {1995}, month = {1995 Feb 10}, pages = {902-5}, abstract = {

The neural basis of sexual orientation in Drosophila was studied by the production of males with regionally feminized brains. Such flies express the female form of the sex determination gene transformer in a limited number of neurons under the control of GAL4 enhancer trap inserts. This method facilitated the creation of lines with a stable pattern of feminization. In tests of sexual preferences, flies that were feminized in a portion of the antennal lobes or in a subset of the corpora pedunculata (mushroom bodies) courted both males and females. These two brain structures, both of which are involved in olfactory processing, may function in the recognition of sex-specific pheromones, in the control of sex-specific behaviors, or both.

}, keywords = {Animals, Bisexuality, Brain, Drosophila melanogaster, Female, Genes, Insect, Male, Sex Attractants, Sexual Behavior, Animal, Smell}, issn = {0036-8075}, author = {Ferveur, J F and St{\"o}rtkuhl, K F and Stocker, R F and Greenspan, R J} } @article {155, title = {Understanding the genetic construction of behavior.}, journal = {Sci Am}, volume = {272}, year = {1995}, month = {1995 Apr}, pages = {72-8}, keywords = {Animals, Drosophila melanogaster, Female, Genetics, Behavioral, Humans, Male, Sexual Behavior, Animal}, issn = {0036-8733}, author = {Greenspan, R J} }