title: Bmp15 Is an Oocyte-Produced Signal Required for Maintenance of the Adult Female Sexual Phenotype in Zebrafish.
abstract: Although the zebrafish is a major model organism, how they determine sex is not well understood. In domesticated zebrafish, sex determination appears to be polygenic, being influenced by multiple genetic factors that may vary from strain to strain, and additionally can be influenced by environmental factors. However, the requirement of germ cells for female sex determination is well documented: animals that lack germ cells, or oocytes in particular, develop exclusively as males. Recently, it has been determined that oocytes are also required throughout the adult life of the animal to maintain the differentiated female state. How oocytes control sex differentiation and maintenance of the sexual phenotype is unknown. We therefore generated targeted mutations in genes for two oocyte produced signaling molecules, Bmp15 and Gdf9 and here report a novel role for Bmp15 in maintaining adult female sex differentiation in zebrafish. Females deficient in Bmp15 begin development normally but switch sex during the mid- to late- juvenile stage, and become fertile males. Additionally, by generating mutations in the aromatase cyp19a1a, we show that estrogen production is necessary for female development and that the function of Bmp15 in female sex maintenance is likely linked to the regulation of estrogen biosynthesis via promoting the development of estrogen-producing granulosa cells in the oocyte follicle.
authors.affiliation: Department of Molecular and Cellular Biology, University of California Davis, Davis, California, United States of America.
authors.forename: Daniel B
authors.identifier: 0000-0002-5685-3833
authors.initials: DB
authors.lastname: Dranow
authors.affiliation: Department of Molecular and Cellular Biology, University of California Davis, Davis, California, United States of America.
authors.forename: Kevin
authors.initials: K
authors.lastname: Hu
authors.affiliation: Department of Molecular and Cellular Biology, University of California Davis, Davis, California, United States of America.
authors.forename: April M
authors.identifier: 0000-0003-3552-072X
authors.initials: AM
authors.lastname: Bird
authors.affiliation: Department of Molecular and Cellular Biology, University of California Davis, Davis, California, United States of America.
authors.forename: S Terese
authors.initials: ST
authors.lastname: Lawry
authors.affiliation: Department of Molecular and Cellular Biology, University of California Davis, Davis, California, United States of America.
authors.forename: Melissa T
authors.identifier: 0000-0002-3676-0285
authors.initials: MT
authors.lastname: Adams
authors.affiliation: Departments of Pediatrics and Molecular Biology, The University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, United States of America.
authors.forename: Angelica
authors.initials: A
authors.lastname: Sanchez
authors.affiliation: Departments of Pediatrics and Molecular Biology, The University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, United States of America.
authors.forename: James F
authors.initials: JF
authors.lastname: Amatruda
authors.affiliation: Department of Molecular and Cellular Biology, University of California Davis, Davis, California, United States of America.
authors.forename: Bruce W
authors.identifier: 0000-0002-4397-7749
authors.initials: BW
authors.lastname: Draper
mesh_terms: D000818:Animals; D001141:Aromatase / Q000235:genetics / Q000378:metabolism; D055430:Bone Morphogenetic Protein 15 / Q000235:genetics* / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism; D005260:Female; D055429:Growth Differentiation Factor 9 / Q000235:genetics / Q000378:metabolism; D008297:Male; D009154:Mutation; D009865:Oocytes / Q000378:metabolism*; D010641:Phenotype; D019849:Sex Determination Processes / Q000235:genetics*; D015398:Signal Transduction; D015027:Zebrafish / Q000235:genetics / Q000254:growth & development; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D055430:Bone Morphogenetic Protein 15; D004967:Estrogens; D055429:Growth Differentiation Factor 9; D029961:Zebrafish Proteins; D001141:Aromatase; C440729:Cyp19a1a protein, zebrafish