@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 {6269, title = {Doublesex functions early and late in gustatory sense organ development.}, journal = {PLoS One}, volume = {7}, year = {2012}, month = {2012}, pages = {e51489}, abstract = {

Somatic sexual dimorphisms outside of the nervous system in Drosophila melanogaster are largely controlled by the male- and female-specific Doublesex transcription factors (DSX(M) and DSX(F), respectively). The DSX proteins must act at the right times and places in development to regulate the diverse array of genes that sculpt male and female characteristics across a variety of tissues. To explore how cellular and developmental contexts integrate with doublesex (dsx) gene function, we focused on the sexually dimorphic number of gustatory sense organs (GSOs) in the foreleg. We show that DSX(M) and DSX(F) promote and repress GSO formation, respectively, and that their relative contribution to this dimorphism varies along the proximodistal axis of the foreleg. Our results suggest that the DSX proteins impact specification of the gustatory sensory organ precursors (SOPs). DSX(F) then acts later in the foreleg to regulate gustatory receptor neuron axon guidance. These results suggest that the foreleg provides a unique opportunity for examining the context-dependent functions of DSX.

}, keywords = {Animals, Axons, Developmental, DNA-Binding Proteins, Drosophila melanogaster, Drosophila Proteins, Gene Expression Regulation, Neurons, Sense Organs, Sex Characteristics, Taste}, issn = {1932-6203}, doi = {10.1371/journal.pone.0051489}, author = {Mellert, David J and Robinett, Carmen C and Baker, Bruce S} } @article {4973, title = {Transvection is common throughout the Drosophila genome.}, journal = {Genetics}, volume = {191}, year = {2012}, month = {2012 May 29}, pages = {1129-41}, abstract = {

Higher-order genome organization plays an important role in transcriptional regulation. In Drosophila, somatic pairing of homologous chromosomes can lead to transvection, by which the regulatory region of a gene can influence transcription in trans. We observe transvection between transgenes inserted at commonly used phiC31 integration sites in the Drosophila genome. When two transgenes that carry endogenous regulatory elements driving the expression of either LexA or GAL4 are inserted at the same integration site and paired, the enhancer of one transgene can drive or repress expression of the paired transgene. These transvection effects depend on compatibility between regulatory elements and are often restricted to a subset of cell types within a given expression pattern. We further show that activated UAS-transgenes can also drive transcription in trans. We discuss the implication of these findings for 1) understanding the molecular mechanisms that underlie transvection and 2) the design of experiments that utilize site-specific integration.

}, issn = {1943-2631}, doi = {10.1534/genetics.112.140475}, author = {Mellert, David J and Truman, James W} } @article {3359, title = {Functional dissection of the neural substrates for sexual behaviors in Drosophila melanogaster.}, journal = {Genetics}, volume = {189}, year = {2011}, month = {2011 Jun 24}, pages = {195-211}, abstract = {

The male-specific Fruitless proteins (Fru(M)) act to establish the potential for male courtship behavior in Drosophila melanogaster and are expressed in small groups of neurons throughout the nervous system. We screened \ 1000 GAL4 lines, using assays for general courtship, male-male interactions, and male fertility to determine the phenotypes resulting from the GAL4 driven inhibition of Fru(M) expression in subsets of these neurons. A battery of secondary assays showed that the phenotypic classes of GAL4 lines could be divided into subgroups based on additional neurobiological and behavioral criteria. For example, in some lines restoration of Fru(M) expression in cholinergic neurons restores fertility or reduces male-male courtship. Persistent chains of males courting each other in some lines results from males courting both sexes indiscriminately whereas in other lines this phenotype result from apparent habituation deficits. Inhibition of ectopic Fru(M) expression in females, in populations of neurons where Fru(M) is necessary for male fertility, can rescue female infertility. To identify the neurons responsible for some of the observed behavioral alterations, we determined the overlap between the identified GAL4 lines and endogenous Fru(M) expression in lines with fertility defects. The GAL4 lines causing fertility defects generally had widespread overlap with Fru(M) expression in many regions of the nervous system suggesting likely redundant Fru(M)-expressing neuronal pathways capable of conferring male fertility. From associations between the screened behaviors, we propose a functional model for courtship initiation.

}, issn = {1943-2631}, doi = {10.1534/genetics.111.129940}, author = {Meissner, Geoffrey W and Manoli, Devanand S and Chavez, Jose F and Knapp, Jon-Michael and Lin, Tasha L and Stevens, Robin J and Mellert, David J and Tran, David H and Baker, Bruce S} } @article {2540, title = {Midline crossing by gustatory receptor neuron axons is regulated by fruitless, doublesex and the roundabout receptors.}, journal = {Development}, volume = {137}, year = {2010}, month = {2010 Jan}, pages = {323-32}, abstract = {

Although nervous system sexual dimorphisms are known in many species, relatively little is understood about the molecular mechanisms generating these dimorphisms. Recent findings in Drosophila provide the tools for dissecting how neurogenesis and neuronal differentiation are modulated by the Drosophila sex-determination regulatory genes to produce nervous system sexual dimorphisms. Here we report studies aimed at illuminating the basis of the sexual dimorphic axonal projection patterns of foreleg gustatory receptor neurons (GRNs): only in males do GRN axons project across the midline of the ventral nerve cord. We show that the sex determination genes fruitless (fru) and doublesex (dsx) both contribute to establishing this sexual dimorphism. Male-specific Fru (Fru(M)) acts in foreleg GRNs to promote midline crossing by their axons, whereas midline crossing is repressed in females by female-specific Dsx (Dsx(F)). In addition, midline crossing by these neurons might be promoted in males by male-specific Dsx (Dsx(M)). Finally, we (1) demonstrate that the roundabout (robo) paralogs also regulate midline crossing by these neurons, and (2) provide evidence that Fru(M) exerts its effect on midline crossing by directly or indirectly regulating Robo signaling.

}, keywords = {Animals, Axons, Cell Surface, Confocal, DNA-Binding Proteins, Drosophila melanogaster, Drosophila Proteins, Female, Immunologic, Male, Microscopy, Nerve Tissue Proteins, Neurons, Receptors, Sex Characteristics, Transcription Factors}, issn = {1477-9129}, doi = {10.1242/dev.045047}, author = {Mellert, David J and Knapp, Jon-Michael and Manoli, Devanand S and Meissner, Geoffrey W and Baker, Bruce S} }