title: Divergent expression regulation of gonad development genes in medaka shows incomplete conservation of the downstream regulatory network of vertebrate sex determination.
abstract: Genetic control of male or female gonad development displays between different groups of organisms a remarkable diversity of "master sex-determining genes" at the top of the genetic hierarchies, whereas downstream components surprisingly appear to be evolutionarily more conserved. Without much further studies, conservation of sequence has been equalized to conservation of function. We have used the medaka fish to investigate the generality of this paradigm. In medaka, the master male sex-determining gene is dmrt1bY, a highly conserved downstream regulator of sex determination in vertebrates. To understand its function in orchestrating the complex gene regulatory network, we have identified targets genes and regulated pathways of Dmrt1bY. Monitoring gene expression and interactions by transgenic fluorescent reporter fish lines, in vivo tissue-chromatin immunoprecipitation and in vitro gene regulation assays revealed concordance but also major discrepancies between mammals and medaka, notably amongst spatial, temporal expression patterns and regulations of the canonical Hedgehog and R-spondin/Wnt/Follistatin signaling pathways. Examination of Foxl2 protein distribution in the medaka ovary defined a new subpopulation of theca cells, where ovarian-type aromatase transcriptional regulation appears to be independent of Foxl2. In summary, these data show that the regulation of the downstream regulatory network of sex determination is less conserved than previously thought.
authors.affiliation: University of Wuerzburg, Physiological Chemistry, Biocenter, Am Hubland, Wuerzburg, Germany.
authors.forename: Amaury
authors.initials: A
authors.lastname: Herpin
authors.forename: Mateus C
authors.initials: MC
authors.lastname: Adolfi
authors.forename: Barbara
authors.initials: B
authors.lastname: Nicol
authors.forename: Maria
authors.initials: M
authors.lastname: Hinzmann
authors.forename: Cornelia
authors.initials: C
authors.lastname: Schmidt
authors.forename: Johanna
authors.initials: J
authors.lastname: Klughammer
authors.forename: Mareen
authors.initials: M
authors.lastname: Engel
authors.forename: Minoru
authors.initials: M
authors.lastname: Tanaka
authors.forename: Yann
authors.initials: Y
authors.lastname: Guiguen
authors.forename: Manfred
authors.initials: M
authors.lastname: Schartl
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001141:Aromatase / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D002460:Cell Line; D019143:Evolution, Molecular; D005260:Female; D029941:Fish Proteins / Q000235:genetics / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D006066:Gonads / Q000378:metabolism*; D006107:Granulosa Cells / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009990:Oryzias / Q000235:genetics* / Q000378:metabolism; D019849:Sex Determination Processes / Q000235:genetics*; D013799:Theca Cells / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D060449:Wnt Signaling Pathway
chemical_list: C110547:DMRT1 protein; D029941:Fish Proteins; D051858:Forkhead Transcription Factors; D008565:Membrane Proteins; D014157:Transcription Factors; D001141:Aromatase
keywords: adaptive evolution; divergent expression regulation; gene regulatory network evolution; gonadal development