No abstract

Normal sexual differentiation in the genital organs is essential for the animal species that use sexual reproduction. Although it is known that doublesex (dsx) is required for the sexual development of the genitalia in various insect species, the direct target genes responsible for the sexual differentiation of the genitalia have not been identified. The lozenge (lz) gene is expressed in the female genital disc and is essential for developments of spermathecae and accessory glands in Drosophila melanogaster. The female-specific isoform of DSX (DSXF) is required for activating lz expression in the female genital disc. However, it still remains unclear whether the DSXF directly activates the transcription of lz in the female genital disc. In this study, we found two sequences (lz-DBS1 and lz-DBS2) within lz locus that showed high homoloty to the DSX binding motif identified previously. Competition assays using recombinant DSX DNA-binding domain (DSX-DBD) protein verified that the DSX-DBD protein bound to lz-DBS1 and lz-DBS2 in a sequence-specific manner with lower affinity than to the known DSX binding site in the bric-à-brac 1 (bab1) gene. Reporter gene analyses revealed that a 2.5-kbp lz genomic fragment containing lz-DBS1 and lz-DBS2 drove reporter gene (EGFP) expression in a manner similar to endogenous lz expression in the female genital disc. Mutations in lz-DBS1 alone significantly reduced the area of EGFP-expressing region, while EGFP expression in the female genital disc was abolished when both sites were mutated. These results demonstrated that DSX directly activates female-specific lz expression in the genital disc through lz-DBS1 and lz-DBS2.

Odorants are detected by olfactory sensory neurons, which are covered by olfactory mucus. Despite the existence of studies on olfactory mucus, its constituents, functions, and interindividual variability remain poorly understood. Here, we describe a human study that combined the collection of olfactory mucus and olfactory psychophysical tests. Our analyses revealed that olfactory mucus contains high concentrations of solutes, such as total proteins, inorganic elements, and molecules for xenobiotic metabolism. The high concentrations result in a capacity to capture or metabolize a specific repertoire of odorants. We provide evidence that odorant metabolism modifies our sense of smell. Finally, the amount of olfactory mucus decreases in an age-dependent manner. A follow-up experiment recapitulated the importance of the amount of mucus in the sensitive detection of odorants by their receptors. These findings provide a comprehensive picture of the molecular processes in olfactory mucus and propose a potential cause of olfactory decline.