Bmp15 Is an Oocyte-Produced Signal Required for Maintenance of the Adult Female Sexual Phenotype in Zebrafish.

Bmp15 Is an Oocyte-Produced Signal Required for Maintenance of the Adult Female Sexual Phenotype in Zebrafish.
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BMP15是维持斑马鱼中成年女性性表型所需的卵母细胞产生的信号。

DOI:
10.1371/journal.pgen.1006323
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发表时间:
2016-09
期刊:
影响因子:
4.5
通讯作者:
Draper BW
Draper BW
中科院分区:
生物学2区
文献类型:
--
作者:
Dranow DB;Hu K;Bird AM;Lawry ST;Adams MT;Sanchez A;Amatruda JF;Draper BW

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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. Domesticated zebrafish use a polygenic mechanism for sex determination, where oocytes play a key role in both promoting primary female sex determination and maintenance of female sex in adults. All animals that cannot produce oocytes during the larval stage develop as males and adult females that cease oocyte production readily sex revert to a male phenotype. These results have led to the hypothesis that oocytes produce a signal that instructs the somatic gonad to develop as an ovary and to suppress testis development. In this report we present evidence that the oocyte-produced signaling protein Bmp15 is required for females to maintain their sexual phenotype, but plays no role in primary female sex determination. Specifically, zebrafish bmp15 mutants can initially develop as females, but during the juvenile stage they sex revert to fertile males. In addition, we show that the ovary-expressed estrogen- producing enzyme, Cyp19a1a aromatase, is a key somatic gonad-produced protein that promotes female development. Our results define for the first time, specific genetic components of the mechanism by which zebrafish promote and maintain their sex, and may also provide insight into the mechanism(s) that allows 2% of all teleost species to reverse their sex as adults.
DOI: 10.1093/bfgp/elt041
发表时间: 2014-03
影响因子: 4
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