title: Sex determination in Drosophila melanogaster and Musca domestica converges at the level of the terminal regulator doublesex.
abstract: Sex-determining cascades are supposed to have evolved in a retrograde manner from bottom to top. Wilkins' 1995 hypothesis finds support from our comparative studies in Drosophila melanogaster and Musca domestica, two dipteran species that separated some 120 million years ago. The sex-determining cascades in these flies differ at the level of the primary sex-determining signal and their targets, Sxl in Drosophila and F in Musca. Here we present evidence that they converge at the level of the terminal regulator, doublesex ( dsx), which conveys the selected sexual fate to the differentiation genes. The dsx homologue in Musca, Md-dsx, encodes male-specific (MdDSX(M)) and female-specific (MdDSX(F)) protein variants which correspond in structure to those in Drosophila. Sex-specific regulation of Md-dsx is controlled by the switch gene F via a splicing mechanism that is similar but in some relevant aspects different from that in Drosophila. MdDSX(F) expression can activate the vitellogenin genes in Drosophila and Musca males, and MdDSX(M) expression in Drosophila females can cause male-like pigmentation of posterior tergites, suggesting that these Musca dsx variants are conserved not only in structure but also in function. Furthermore, downregulation of Md-dsx activity in Musca by injecting dsRNA into embryos leads to intersexual differentiation of the gonads. These results strongly support a role of Md-dsx as the final regulatory gene in the sex-determining hierarchy of the housefly.
authors.affiliation: Zoological Institute, University Zürich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
authors.forename: Monika
authors.initials: M
authors.lastname: Hediger
authors.forename: Géza
authors.initials: G
authors.lastname: Burghardt
authors.forename: Christina
authors.initials: C
authors.lastname: Siegenthaler
authors.forename: Nathalie
authors.initials: N
authors.lastname: Buser
authors.forename: Denise
authors.initials: D
authors.lastname: Hilfiker-Kleiner
authors.forename: Andreas
authors.initials: A
authors.lastname: Dübendorfer
authors.forename: Daniel
authors.initials: D
authors.lastname: Bopp
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D005075:Biological Evolution; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D014644:Genetic Variation / Q000235:genetics; D006793:Houseflies / Q000196:embryology* / Q000235:genetics* / Q000378:metabolism; D019476:Insect Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D034622:RNA Interference; D022821:RNA Splice Sites / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D038621:Regulatory Sequences, Ribonucleic Acid / Q000235:genetics; D017385:Sequence Homology; D012727:Sex Characteristics; D019849:Sex Determination Processes; D012733:Sex Differentiation / Q000235:genetics; D014819:Vitellogenins / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C070369:DSX protein, Drosophila; D029721:Drosophila Proteins; D019476:Insect Proteins; D022821:RNA Splice Sites; D012333:RNA, Messenger; D038621:Regulatory Sequences, Ribonucleic Acid; D014819:Vitellogenins