Project description:Autism spectrum disorders (ASD) are ~4-times more common in males than females, and CHD8 (a chromatin remodeler)-related ASD shows a strong male bias (~4:1), although the underlying mechanism remains unclear. Chd8-mutant mice with a C-terminal protein-truncating mutation (N2373K) display male-preponderant behavioral deficits as juveniles and adults, although whether this also applies to other Chd8 mutations remains unknown. In addition, it remains unclear whether sexually dimorphic phenotypes in Chd8-mutant mice are differentially observed in males and females across different ages. We here generated new Chd8-mutant (knock-in) mice carrying a patient-derived mutation causing an N-terminal and stronger protein truncation (Chd8+/S62X mice) and characterized the mice by behavioral analyses. Juvenile Chd8+/S62X mice displayed male-preponderant autistic-like behaviors; hypoactivity and enhanced mother-seeking/attachment behavior in males but not in females. Adult male and female Chd8+/S62X mice showed largely similar deficits in repetitive and anxiety-like behavioral domains. Therefore, the CHD8-S62X mutation induces ASD-like behaviors in juvenile male mice and adult male and female mice, pointing to an age-differential sexual dimorphism and also distinct sexual dimorphisms in different Chd8 mutations (N2373K and S62X).
Project description:To further elucidate the roles of germ cells in the sex differentiation of gonads, we have used the medaka, a teleost fish, to generate mutants that lack germ cells from the onset of gonadogenesis by the morpholino-mediated knockdown of cxcr4. The resulting germ-cell-deficient medaka show female-to-male sex reversal of their secondary sex characteristics, accompanied by increased levels of androgen and reduced levels of estrogen. A failure to maintain granulosa cells or estrogen-producing cells also occurs at early stages of sex differentiation in the cxcr4 morphants, before the initiation of gonadal morphogenesis. In contrast, androgen-producing cells are unaffected in germ-cell-deficient medaka of either sex. In addition, a single tube-like gonad that expresses male-specific genes is formed in these mutants irrespective of the genetic sex. Significantly, each of these mutant phenotypes occurs in a somatic cell-autonomous manner, suggesting that gonadal somatic cells are predisposed toward male development in the absence of germ cells. This highlights the importance of germ cells in the sexual dimorphism of the gonads.
Project description:In the present study, we utilized a label-free proteomics approach to identify and quantify proteins that are the basis of sexual dimorphism in the GI tract of zebrafish. The results of present study in combination with an extensive literature review can provide an in-depth insight into the molecular mechanisms that distinguish sexes in the digestion and absorption of nutritional materials needed for body maintenance and gametogenesis, as well as their abilities for drug metabolism.
Project description:The present study aims to apply a high-resolution and label-free proteomics approach to identify and quantify proteins in the eye of zebrafish. First, the results of the present study will provide a comprehensive list of proteins in the eye of zebrafish, and second, establish a platform based on sex-biased proteins that may offer clues to answer crucial questions such as sex-based differences in visual perception and impairments. Our results may improve the outcome of behavioural, developmental, toxicological, and medical experiments considering the zebrafish eye.
Project description:In the present study we used a proteomic approach to identify and quantify protein abundance differences between male and female zebrafish heart to explore, at the molecular level, any possible sex-biased differences in the heart as the central part of the cardiovascular system for this model organism. The results from the study provide a novel and wide proteome resource, which could be further used to study the role of the identified proteins in the cardiovascular system in both sexes. Furthermore, we hope that this study may open a new window towards the development of sex and gender-based drugs and it establishes sex as a factor to be considered when designing toxicological experiments.
Project description:Doublesex (Dsx) and Fruitless (Fru) are the two downstream transcription factors that actuate Drosophila sex determination. While Dsx assists Fru to regulate sex-specific behavior, whether Fru collaborates with Dsx in regulating other aspects of sexual dimorphism remains unknown. One important aspect of sexual dimorphism is found in the gonad stem cell (GSC) niches, where male and female GSCs are regulated to create large numbers of sperm and eggs. Here we report that Fru is expressed male-specifically in the GSC niche and plays important roles in the development and maintenance of these cells. Unlike previously-studied aspects of sex-specific Fru expression, which are regulated by Transformer (Tra)-mediated alternative splicing, we show that male-specific expression of fru in the gonad is regulated downstream of dsx, and is independent of tra. fru genetically interacts with dsx to support maintenance of the niche throughout development. Ectopic expression of fru inhibited female niche formation and partially masculinized the ovary. fru is also required autonomously for cyst stem cell maintenance and cyst cell survival. Finally, we identified a conserved Dsx binding site upstream of fru promoter P4 that regulates fru expression in the niche, indicating that fru is likely a direct target for transcriptional regulation by Dsx. These findings demonstrate that fru acts outside the nervous system to influence sexual dimorphism and reveal a new mechanism for regulating sex-specific expression of fru that is regulated at the transcriptional level by Dsx, rather than by alternative splicing by Tra.
Project description:BackgroundSex-specific behavior may originate from differences in brain structure or function. In Drosophila, the action of the male-specific isoform of fruitless in about 2000 neurons appears to be necessary and sufficient for many aspects of male courtship behavior. Initial work found limited evidence for anatomical dimorphism in these fru+ neurons. Subsequently, three discrete anatomical differences in central brain fru+ neurons have been reported, but the global organization of sex differences in wiring is unclear.ResultsA global search for structural differences in the Drosophila brain identified large volumetric differences between males and females, mostly in higher brain centers. In parallel, saturating clonal analysis of fru+ neurons using mosaic analysis with a repressible cell marker identified 62 neuroblast lineages that generate fru+ neurons in the brain. Coregistering images from male and female brains identified 19 new dimorphisms in males; these are highly concentrated in male-enlarged higher brain centers. Seven dimorphic lineages also had female-specific arbors. In addition, at least 5 of 51 fru+ lineages in the nerve cord are dimorphic. We use these data to predict >700 potential sites of dimorphic neural connectivity. These are particularly enriched in third-order olfactory neurons of the lateral horn, where we provide strong evidence for dimorphic anatomical connections by labeling partner neurons in different colors in the same brain.ConclusionOur analysis reveals substantial differences in wiring and gross anatomy between male and female fly brains. Reciprocal connection differences in the lateral horn offer a plausible explanation for opposing responses to sex pheromones in male and female flies.
Project description:BackgroundSexual size dimorphism (SSD) is widespread and variable among animals. Sexual selection, fecundity selection and ecological divergence between males and females are the major evolutionary forces of SSD. However, the influences of mating system and habitat types on SSD have received little attention. Here, using phylogenetic comparative methods, we at first examine the hypotheses to that mating system (intensity of sexual selection) and habitat types affect significantly variation in SSD in anurans (39 species and 18 genera).ResultsOur data set encompass 39 species with female-biased SSD. We provide evidence that the effects of mating system and habitat types on SSD were non-significant across species, also when the analyses were phylogenetically corrected.ConclusionsContrast to the hypotheses, our findings suggest that mating system and habitat types do not play an important role in shaping macro-evolutionary patterns of SSD in anurans. Mating system and habitat types cannot explain the variation in SSD when correcting for phylogenetic effects.
Project description:Evidence for phenotypic plasticity in brain size and the size of different brain parts is widespread, but experimental investigations into this effect remain scarce and are usually conducted using individuals from a single population. As the costs and benefits of plasticity may differ among populations, the extent of brain plasticity may also differ from one population to another. In a common garden experiment conducted with three-spined sticklebacks (Gasterosteus aculeatus) originating from four different populations, we investigated whether environmental enrichment (aquaria provided with structural complexity) caused an increase in the brain size or size of different brain parts compared to controls (bare aquaria). We found no evidence for a positive effect of environmental enrichment on brain size or size of different brain parts in either of the sexes in any of the populations. However, in all populations, males had larger brains than females, and the degree of sexual size dimorphism (SSD) in relative brain size ranged from 5.1 to 11.6% across the populations. Evidence was also found for genetically based differences in relative brain size among populations, as well as for plasticity in the size of different brain parts, as evidenced by consistent size differences among replicate blocks that differed in their temperature.
Project description:Female but not male mosquitoes are vectors for multiple deadly human diseases including malaria, dengue, yellow fever, and West Nile virus. However, the underlying neural substrates of sexually dimorphic behaviors remain largely unknown in mosquitoes. In this study, we found striking sexual dimorphism in brain regions in two major disease vectors, Aedes aegypti and Culex quinquefasciatus, through voxel-wise comparison of the whole brain. Female-enlarged regions include those associated with chemosensation and vision, while male-enlarged regions are linked to hearing and memory. However, some brain regions associated with vision and memory are sexually dimorphic in A e . aegypti but not C x . quinquefasciatus. As the first global voxel-based comparative neuroanatomical analysis of mosquito brains between sexes, this study not only sheds light on the neural substrates underlying sex-specific behaviors, but also identifies regions of interest for future research to disrupt female-specific behaviors critical to disease transmission.