BackgroundTeleost fishes exhibit remarkably diverse and plastic sexual developmental patterns. One of the most astonishing is the rapid socially controlled female-to-male (protogynous) sex change observed in bluehead wrasses (Thalassoma bifasciatum). Such functional sex change is widespread in marine fishes, including species of commercial importance, yet its underlying molecular basis remains poorly explored.MethodsRNA sequencing was performed to characterize the transcriptomic profiles and identify genes exhibiting sex-biased expression in the brain (forebrain and midbrain) and gonads of bluehead wrasses. Functional annotation and enrichment analysis were carried out for the sex-biased genes in the gonad to detect global differences in gene products and genetic pathways between males and females.ResultsHere we report the first transcriptomic analysis for a protogynous fish. Expression comparison between males and females reveals a large set of genes with sex-biased expression in the gonad, but relatively few such sex-biased genes in the brain. Functional annotation and enrichment analysis suggested that ovaries are mainly enriched for metabolic processes and testes for signal transduction, particularly receptors of neurotransmitters and steroid hormones. When compared to other species, many genes previously implicated in male sex determination and differentiation pathways showed conservation in their gonadal expression patterns in bluehead wrasses. However, some critical female-pathway genes (e.g., rspo1 and wnt4b) exhibited unanticipated expression patterns. In the brain, gene expression patterns suggest that local neurosteroid production and signaling likely contribute to the sex differences observed.ConclusionsExpression patterns of key sex-related genes suggest that sex-changing fish predominantly use an evolutionarily conserved genetic toolkit, but that subtle variability in the standard sex-determination regulatory network likely contributes to sexual plasticity in these fish. This study not only provides the first molecular data on a system ideally suited to explore the molecular basis of sexual plasticity and tissue re-engineering, but also sheds some light on the evolution of diverse sex determination and differentiation systems.Electronic supplementary materialThe online version of this article (doi:10.1186/s13293-015-0044-8) contains supplementary material, which is available to authorized users.

Bluehead wrasses undergo dramatic, socially cued female-to-male sex change. We apply transcriptomic and methylome approaches in this wild coral reef fish to identify the primary trigger and subsequent molecular cascade of gonadal metamorphosis. Our data suggest that the environmental stimulus is exerted via the stress axis and that repression of the aromatase gene (encoding the enzyme converting androgens to estrogens) triggers a cascaded collapse of feminizing gene expression and identifies notable sex-specific gene neofunctionalization. Furthermore, sex change involves distinct epigenetic reprogramming and an intermediate state with altered epigenetic machinery expression akin to the early developmental cells of mammals. These findings reveal at a molecular level how a normally committed developmental process remains plastic and is reversed to completely alter organ structures.

BackgroundAnimals experience stress in many contexts and often successfully cope. Individuals exhibiting the proactive versus reactive stress coping styles display qualitatively different behavioral and neuroendocrine responses to stressors. The predisposition to exhibiting a particular coping style is due to genetic and environmental factors. In this study we explore the neurotranscriptomic and gene network biases that are associated with differences between zebrafish (Danio rerio) lines selected for proactive and reactive coping styles and reared in a common garden environment.ResultsUsing RNA-sequencing we quantified the basal transcriptomes from the brains of wild-derived zebrafish lines selectively bred to exhibit the proactive or reactive stress coping style. We identified 1953 genes that differed in baseline gene expression levels. Weighted gene coexpression network analyses identified one gene module associated with line differences. Together with our previous pharmacological experiment, we identified a core set of 62 genes associated with line differences. Gene ontology analyses reveal that many of these core genes are implicated in neurometabolism (e.g. organic acid biosynthetic and fatty acid metabolic processes).ConclusionsOur results show that proactive and reactive stress coping individuals display distinct basal neurotranscriptomic states. Differences in baseline expression of select genes or regulation of specific gene modules are linked to the magnitude of the behavioral response and the display of a coping style, respectively. Our results expand the molecular mechanisms of stress coping from one focused on the neurotransmitter systems to a more complex system that involves an organism’s capability to handle neurometabolic loads and allows for comparisons with other animal taxa to uncover potential conserved mechanisms.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1626-x) contains supplementary material, which is available to authorized users.

SUMMARYTeleost fish exhibit remarkably diverse and plastic patterns of sexual development. One of the most fascinating modes of plasticity is functional sex change, which is widespread in marine fish including species of commercial importance; however, the regulatory mechanisms remain elusive. In this review, we explore such sexual plasticity in fish, using the bluehead wrasse (Thalassoma bifasciatum) as the primary model. Synthesizing current knowledge, we propose that cortisol and key neurochemicals modulate gonadotropin releasing hormone and luteinizing hormone signaling to promote socially controlled sex change in protogynous fish. Future largescale genomic analyses and systematic comparisons among species, combined with manipulation studies, will likely uncover the common and unique pathways governing this astonishing transformation. Revealing the molecular and neuroendocrine mechanisms underlying sex change in fish will greatly enhance our understanding of vertebrate sex determination and differentiation as well as phenotypic plasticity in response to environmental influences.

Socially-controlled functional sex change in fishes is a dramatic example of adaptive reproductive plasticity. Functional gonadal sex change can occur within a week while behavioral sex change can begin within minutes. Significant progress has been made in understanding the neuroendocrine bases of this phenomenon at both the gonadal and the neurobiological levels, but a detailed mechanistic understanding remains elusive. We are working with sex-changing wrasses to identify evolutionarily-conserved neuroendocrine pathways underlying this reproductive adaptation. One key model is the bluehead wrasse (Thalassoma bifasciatum), in which sex change is well studied at the behavioral, ecological, and neuroendocrine levels. Bluehead wrasses show rapid increases in aggressive and courtship behaviors with sex change that do not depend on the presence of gonads. The display of male-typical behavior is correlated with the expression of arginine vasotocin, and experiments support a role for this neuropeptide. Estrogen synthesis is also critical in the process. Female bluehead wrasses have higher abundance of aromatase mRNA in the brain and gonads, and estrogen implants block behavioral sex change. While established methods have advanced our understanding of sex change, a full understanding will require new approaches and perspectives. First, contributions of other neuroendocrine systems should be better characterized, particularly glucocorticoid and thyroid signaling. Second, advances in genomics for non-traditional model species should allow conserved mechanisms to be identified with a key next-step being manipulative tests of these mechanisms. Finally, advances in genomics now also allow study of the role of epigenetic modifications and other regulatory mechanisms in the dramatic alterations across the sex-change process.