title: Opposite roles of DMRT1 and its W-linked paralogue, DM-W, in sexual dimorphism of Xenopus laevis: implications of a ZZ/ZW-type sex-determining system.
abstract: A Y-linked gene, DMY/dmrt1bY, in teleost fish medka and a Z-linked gene, DMRT1, in chicken are both required for male sex determination. We recently isolated a W-linked gene, DM-W, as a paralogue of DMRT1 in Xenopus laevis, which has a ZZ/ZW-type sex-determining system. The DNA-binding domain of DM-W shows high sequence identity with that of DMRT1, but DM-W has no significant sequence similarity with the transactivation domain of DMRT1. Here, we first show colocalization of DM-W and DMRT1 in the somatic cells surrounding primordial germ cells in ZW gonad during sex determination. We next examined characteristics of DM-W and DMRT1 as a transcription factor in vitro. DM-W and DMRT1 shared a DNA-binding sequence. Importantly, DM-W dose-dependently antagonized the transcriptional activity of DMRT1 on a DMRT1-driven luciferase reporter system in 293 cells. We also examined roles of DM-W or DMRT1 in gonadal formation. Some transgenic ZW tadpoles bearing a DM-W knockdown vector had gonads with a testicular structure, and two developed into frogs with testicular gonads. Ectopic DMRT1 induced primary testicular development in some ZW individuals. These observations indicated that DM-W and DMRT1 could have opposite functions in the sex determination. Our findings support a novel model for a ZZ/ZW-type system in which DM-W directs female sex as a sex-determining gene, by antagonizing DMRT1. Additionally, they suggest that DM-W diverged from DMRT1 as a dominant-negative type gene, i.e. as a ;neofunctionalization' gene for the ZZ/ZW-type system. Finally, we discuss a conserved role of DMRT1 in testis formation during vertebrate evolution.
authors.affiliation: Department of Bioscience, School of Science, Kitasato University, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Yoshimoto
authors.forename: Nozomi
authors.initials: N
authors.lastname: Ikeda
authors.forename: Yumi
authors.initials: Y
authors.lastname: Izutsu
authors.forename: Tadayoshi
authors.initials: T
authors.lastname: Shiba
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Takamatsu
authors.forename: Michihiko
authors.initials: M
authors.lastname: Ito
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005799:Genes, Dominant; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D010053:Ovary / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D012730:Sex Chromosomes; D019849:Sex Determination Processes; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*; D015533:Transcriptional Activation; D029867:Xenopus Proteins / Q000378:metabolism / Q000502:physiology*
chemical_list: C551581:DM-W protein, Xenopus; C110547:DMRT1 protein; D004268:DNA-Binding Proteins; D014157:Transcription Factors; D029867:Xenopus Proteins