@article {67950, title = {Regulation of Drosophila courtship behavior by the Tlx/tailless-like nuclear receptor, dissatisfaction.}, journal = {Current Biology}, volume = {32}, year = {2022}, month = {2022 Apr 25}, pages = {1703-1714}, abstract = {

Sexually dimorphic courtship behaviors in Drosophila melanogaster develop from the activity of the sexual differentiation genes, doublesex (dsx) and fruitless (fru), functioning with other regulatory factors that have received little attention. The dissatisfaction (dsf) gene encodes an orphan nuclear receptor homologous to vertebrate Tlx and Drosophila tailless that is critical for the development of several aspects of female- and male-specific sexual behaviors. Here, we report the pattern of dsf expression in the central nervous system and show that the activity of sexually dimorphic abdominal interneurons that co-express dsf and dsx is necessary and sufficient for vaginal plate opening in virgin females, ovipositor extrusion in mated females, and abdominal curling in males during courtship. We find that dsf activity results in different neuroanatomical outcomes in females and males, promoting and suppressing, respectively, female development and function of these neurons depending upon the sexual state of dsx expression. We posit that dsf and dsx interact to specify sex differences in the neural circuitry for dimorphic abdominal behaviors.

}, issn = {1879-0445}, doi = {10.1016/j.cub.2022.02.031}, author = {Duckhorn, Julia C and Cande, Jessica and Metkus, Mary C and Song, Hyeop and Altamirano, Sofia and Stern, David L and Shirangi, Troy R} } @article {48657, title = {A systematic nomenclature for the Drosophila ventral nervous system.}, journal = {bioRxiv}, year = {2017}, month = {2017 Apr 26}, abstract = {

Insect nervous systems are proven and powerful model systems for neuroscience research with wide relevance in biology and medicine. However, descriptions of insect brains have suffered from a lack of a complete and uniform nomenclature. Recognising this problem the Insect Brain Name Working Group produced the first agreed hierarchical nomenclature system for the adult insect brain, using Drosophila melanogaster as the reference framework, with other insect taxa considered to ensure greater consistency and expandability (Ito et al., 2014). Ito et al. (2014) purposely focused on the gnathal regions that account for approximately 50\% of the adult CNS. We extend this nomenclature system to the sub-gnathal regions of the adult Drosophila nervous system to provide a nomenclature of the so-called ventral nervous system (VNS), which includes the thoracic and abdominal neuromeres that was not included in the original work and contains the neurons that play critical roles underpinning most fly behaviours.

}, doi = {10.1101/122952}, author = {Court, Robert Christopher and Armstrong, James Douglas and Borner, Jana and Card, Gwyneth M and Costa, Marta and Dickinson, Michael H and Duch, Carsten and Korff, Wyatt and Mann, Richard S and Merritt, David and Murphey, Rodney K and Namiki, Shigehiro and Seeds, Andrew M and Shepherd, David and Shirangi, Troy R and Simpson, Julie H and Truman, James W and Tuthill, John C and Williams, Darren W} } @article {47553, title = {Doublesex regulates the connectivity of a neural circuit controlling Drosophila male courtship song.}, journal = {Developmental Cell}, volume = {37}, year = {2016}, month = {2016 Jun 20}, pages = {533-44}, abstract = {

It is unclear how regulatory genes establish neural circuits that compose sex-specific behaviors. The\ Drosophila melanogaster\ male courtship song provides a powerful model to study this problem. Courting males vibrate a wing to sing bouts of pulses and hums, called pulse and sine song, respectively. We report the discovery of male-specific thoracic interneurons{\textemdash}the TN1A neurons{\textemdash}that are required specifically for sine song. The TN1A neurons can drive the activity of a sex-non-specific wing motoneuron,\ hg1, which is also required for sine song. The male-specific connection between the TN1A neurons and the\ hg1\ motoneuron is regulated by the sexual differentiation gene\ doublesex. We find that\ doublesex\ is required in the TN1A neurons during development to increase the density of the TN1A arbors that interact with dendrites of the\ hg1motoneuron. Our findings demonstrate how a sexual differentiation gene can build a sex-specific circuit motif by modulating neuronal arborization.

{\textbullet}Doublesex-expressing TN1 neurons are necessary and sufficient for the male sine song{\textbullet}A subclass of TN1 neurons, TN1A, contributes to the sine song{\textbullet}TN1A neurons are functionally coupled to a sine song motoneuron,\ hg1{\textbullet}Doublesex\ regulates the connectivity between the TN1A and\ hg1\ neurons

It is unclear how developmental regulatory genes specify sex-specific behaviors. Shirangi et\ al. demonstrate that the\ Drosophila\ sexual differentiation gene\ doublesex\ encodes a sex-specific behavior{\textemdash}male song{\textemdash}by promoting the connectivity between the male-specific TN1A neurons and the sex-non-specific\ hg1\ neurons, which are required for production of the song.

}, doi = {10.1016/j.devcel.2016.05.012}, author = {Shirangi, Troy R and Wong, Allen M and Truman, James W and Stern, David L} } @article {47524, title = {Genetic and environmental control of neurodevelopmental robustness in Drosophila.}, journal = {PLoS One}, volume = {11}, year = {2016}, month = {2016 May 25}, pages = {e0155957}, abstract = {

Interindividual differences in neuronal wiring may contribute to behavioral individuality and affect susceptibility to neurological disorders. To investigate the causes and potential consequences of wiring variation in Drosophila melanogaster, we focused on a hemilineage of ventral nerve cord interneurons that exhibits morphological variability. We find that late-born subclasses of the 12A hemilineage are highly sensitive to genetic and environmental variation. Neurons in the second thoracic segment are particularly variable with regard to two developmental decisions, whereas its segmental homologs are more robust. This variability "hotspot" depends on Ultrabithorax expression in the 12A neurons, indicating variability is cell-intrinsic and under genetic control. 12A development is more variable and sensitive to temperature in long-established laboratory strains than in strains recently derived from the wild. Strains with a high frequency of one of the 12A variants also showed a high frequency of animals with delayed spontaneous flight initiation, whereas other wing-related behaviors did not show such a correlation and were thus not overtly affected by 12A variation. These results show that neurodevelopmental robustness is variable and under genetic control in Drosophila and suggest that the fly may serve as a model for identifying conserved gene pathways that stabilize wiring in stressful developmental environments. Moreover, some neuronal lineages are variation hotspots and thus may be more amenable to evolutionary change.

}, issn = {1932-6203}, doi = {10.1371/journal.pone.0155957}, author = {Mellert, David J and Williamson, W Ryan and Shirangi, Troy R and Card, Gwyneth M and Truman, James W} } @article {6671, title = {Motor control of Drosophila courtship song.}, journal = {Cell Reports}, volume = {5}, year = {2013}, month = {2013 Nov 14}, pages = {678-86}, abstract = {

Many animals utilize acoustic signals-or songs-to attract mates. During courtship, Drosophila melanogaster males vibrate a wing to produce trains of pulses and extended tone, called pulse and sine song, respectively. Courtship songs in the genus Drosophila are exceedingly diverse, and different song features appear to have evolved independently of each other. How the nervous system allows such diversity to evolve is not understood. Here, we identify a wing muscle in D.\ melanogaster (hg1) that is uniquely male-enlarged. The hg1 motoneuron and the sexually dimorphic development of the hg1 muscle are required specifically for the sine component of the male song. In contrast, the motoneuron innervating a sexually monomorphic wing muscle, ps1, is required specifically for a feature of pulse song. Thus, individual wing motor pathways can control separate aspects of courtship song and may provide a "modular" anatomical substrate for the evolution of diverse songs.

}, issn = {2211-1247}, doi = {10.1016/j.celrep.2013.09.039}, author = {Shirangi, Troy R and Stern, David L and Truman, James W} } @article {2468, title = {Rapid evolution of sex pheromone-producing enzyme expression in Drosophila.}, journal = {PLoS Biology}, volume = {7}, year = {2009}, month = {2009 Aug 4}, pages = {e1000168}, abstract = {

A wide range of organisms use sex pheromones to communicate with each other and to identify appropriate mating partners. While the evolution of chemical communication has been suggested to cause sexual isolation and speciation, the mechanisms that govern evolutionary transitions in sex pheromone production are poorly understood. Here, we decipher the molecular mechanisms underlying the rapid evolution in the expression of a gene involved in sex pheromone production in Drosophilid flies. Long-chain cuticular hydrocarbons (e.g., dienes) are produced female-specifically, notably via the activity of the desaturase DESAT-F, and are potent pheromones for male courtship behavior in Drosophila melanogaster. We show that across the genus Drosophila, the expression of this enzyme is correlated with long-chain diene production and has undergone an extraordinary number of evolutionary transitions, including six independent gene inactivations, three losses of expression without gene loss, and two transitions in sex-specificity. Furthermore, we show that evolutionary transitions from monomorphism to dimorphism (and its reversion) in desatF expression involved the gain (and the inactivation) of a binding-site for the sex-determination transcription factor, DOUBLESEX. In addition, we documented a surprising example of the gain of particular cis-regulatory motifs of the desatF locus via a set of small deletions. Together, our results suggest that frequent changes in the expression of pheromone-producing enzymes underlie evolutionary transitions in chemical communication, and reflect changing regimes of sexual selection, which may have contributed to speciation among Drosophila.

}, keywords = {Animal, Animal Communication, Animals, Binding Sites, DNA-Binding Proteins, Drosophila, Drosophila Proteins, Evolution, Fatty Acid Desaturases, Female, Gene Expression Regulation, In Situ Hybridization, Male, Mating Preference, Molecular, Sex Attractants, Sex Characteristics, Sexual Behavior}, issn = {1545-7885}, doi = {10.1371/journal.pbio.1000168}, author = {Shirangi, Troy R and Dufour, H{\'e}lo\"{\i}se D and Williams, Thomas M and Carroll, Sean B} } @article {2469, title = {Sex in flies: what {\textquoteright}body{\textendash}mind{\textquoteright} dichotomy?}, journal = {Developmental Biology}, volume = {306}, year = {2007}, month = {2007 Jun 1}, pages = {10-9}, abstract = {

Sexual behavior in Drosophila results from interactions of multiple neural and genetic pathways. Male-specific fruitless (fruM) is a major component inducing male behaviors, but recent work indicates key roles for other sex-specific and sex-non-specific components. Notably, male-like courtship by retained (retn) mutant females reveals an intrinsic pathway for male behavior independent of fruM, while behavioral differences between males and females with equal levels of fruM expression indicate involvement of another sex-specific component. Indeed, sex-specific products of doublesex (dsxF and dsxM), that control sexual differentiation of the body, also contribute to sexual behavior and neural development of both sexes. In addition, the single product of the dissatisfaction (dsf) gene is needed for appropriate behavior in both sexes, implying additional complexities and levels of control. The genetic mechanisms controlling sexual behavior are similar to those controlling body sexual development, suggesting biological advantages of modifying an intermediate intrinsic pathway in generation of two substantially different behavioral or morphological states.

}, keywords = {Animal, Animals, Cytoplasmic and Nuclear, Drosophila, Drosophila Proteins, Female, Genes, Insect, Male, Microtubule-Associated Proteins, Nerve Tissue Proteins, Neurons, Neuropeptides, Receptors, Sex, Sexual Behavior, Transcription Factors}, issn = {0012-1606}, doi = {10.1016/j.ydbio.2007.03.022}, author = {Shirangi, Troy R and McKeown, Michael} } @article {2470, title = {A double-switch system regulates male courtship behavior in male and female Drosophila melanogaster.}, journal = {Nature Genetics}, volume = {38}, year = {2006}, month = {2006 Dec}, pages = {1435-9}, abstract = {

Current models describe male-specific fruitless (fruM) as a genetic {\textquoteright}switch{\textquoteright} regulating sexual behavior in Drosophila melanogaster, and they postulate that female (F) and male (M) doublesex (dsx) products control body sexual morphology. In contradiction to this simple model, we show that dsx, as well as fruM and non-sex-specific retained (retn), affect both male and female sexual behaviors. In females, both retn and dsxF contribute to female receptivity, and both genes act to repress male-like courtship activity in the presence or absence of fruM. In males, consistent with the opposing functions of dsxM and dsxF, dsxM acts as a positive factor for male courtship. retn also acts counter to fruM in the development of the male-specific muscle of Lawrence. Molecularly, retn seems to regulate sexual behavior via a previously described complex that represses zerknullt. Thus, we show that fru and dsx together act as a {\textquoteright}switch{\textquoteright} system regulating behavior in the context of other developmental genes, such as retn.

}, keywords = {Animal, Animals, DNA-Binding Proteins, Drosophila melanogaster, Drosophila Proteins, Female, Gene Expression Regulation, Genes, Homeodomain Proteins, Insect, Male, Mutation, Nerve Tissue Proteins, Nuclear Proteins, Phenotype, Sexual Behavior, Transcription Factors}, issn = {1061-4036}, doi = {10.1038/ng1908}, author = {Shirangi, Troy R and Taylor, Barbara J and McKeown, Michael} } @article {2472, title = {Nuclear degradation of p53 occurs during down-regulation of the p53 response after DNA damage.}, journal = {The FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology}, volume = {16}, year = {2002}, month = {2002 Mar}, pages = {420-2}, abstract = {

The principal regulator of p53 stability is HDM2, an E3 ligase that mediates p53 degradation via the ubiquitin-26S proteasome pathway. The current model holds that p53 degradation occurs exclusively on cytoplasmic proteasomes and hence has an absolute requirement for nuclear export of p53 via the CRM-1 pathway. However, proteasomes are abundant in both cytosol and nucleus, and no studies have been done to determine under what physiological circumstances p53 degradation might occur in the nucleus. We analyzed HDM2-mediated degradation of endogenous p53 in the presence of various nuclear export inhibitors of CRM-1, including leptomycin B (LMB), a noncompetitive, specific, and fast-acting inhibitor; and HTLV1-Rex protein, a potent competitive inhibitor. We found that significant HDM2-mediated p53 degradation took place in the presence of LMB or HTLV1-Rex, indicating that endogenous p53 degradation occurs locally in the nucleus, in parallel to cytoplasmic degradation. Moreover, p53 null cells that coexpressed export-defective mutants of p53 and HDM2 retained partial competence for p53 degradation. It is important that nuclear degradation of p53 occurred during the poststress recovery phase of a p53 response, after DNA damage ceased. We propose that the capability of local p53 degradation within the nucleus provides a tighter and faster control during the down-regulatory phase, when an active p53 program needs to be turned off quickly.

}, keywords = {Active Transport, Animals, Biological, Cell Line, Cell Nucleus, Cytoplasm, DNA Damage, Down-Regulation, Gene Products, Kinetics, Models, Mutation, Nuclear Localization Signals, Nuclear Proteins, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-mdm2, rex, Transfection, Tumor Suppressor Protein p53}, issn = {1530-6860}, doi = {10.1096/fj.01-0617fje}, author = {Shirangi, Troy R and Zaika, Alex and Moll, Ute M} }