부산대학교 도서관

Sex is determined by multiple factors derived from somatic and germ cells in vertebrates. We have identified amhy, dmrt1, gsdf as male and foxl2, foxl3, cyp19a1a as female sex determination pathway genes in Nile tilapia. However, the relationship among these genes is largely unclear. Here, we found that the gonads of dmrt1;cyp19a1a double mutants developed as ovaries or underdeveloped testes with no germ cells irrespective of their genetic sex. In addition, the gonads of dmrt1;cyp19a1a;cyp19a1b triple mutants still developed as ovaries. The gonads of foxl3;cyp19a1a double mutants developed as testes, while the gonads of dmrt1;cyp19a1a;foxl3 triple mutants eventually developed as ovaries. In contrast, the gonads of amhy;cyp19a1a, gsdf;cyp19a1a, amhy;foxl2, gsdf;foxl2 double and amhy;cyp19a1a;cyp19a1b, gsdf;cyp19a1a;cyp19a1b triple mutants developed as testes with spermatogenesis via up-regulation of dmrt1 in both somatic and germ cells. The gonads of amhy;foxl3 and gsdf;foxl3 double mutants developed as ovaries but with germ cells in spermatogenesis due to up-regulation of dmrt1. Taking the respective ovary and underdeveloped testis of dmrt1;foxl3 and dmrt1;foxl2 double mutants reported previously into consideration, we demonstrated that once dmrt1 mutated, the gonad could not be rescued to functional testis by mutating any female pathway gene. The sex reversal caused by mutation of male pathway genes other than dmrt1, including its upstream amhy and downstream gsdf, could be rescued by mutating female pathway gene. Overall, our data suggested that dmrt1 is the only male pathway gene tested indispensable for sex determination and functional testis development in tilapia. Author summary: In vertebrates, the antagonistic effect between male and female pathway genes determines the development of gonads towards ovaries or testes and maintains the final gonadal phenotype. Using tilapia as animal model, we found that the dmrt1 mutant gonad could not be rescued to a functional testis by mutation of female pathway genes foxl2, foxl3 and cyp19a1a. In contrast, the amhy and gsdf mutant gonad can be rescued to functional testis by mutating female pathway genes via up-regulation of dmrt1. Our data strongly highlight the indispensable role of dmrt1 in male sex determination and testicular development. The possible reason is that it is the only sex determining pathway gene identified so far expressing in both germ cells and somatic cells, while others were exclusively expressed in somatic cells or germ cells. This might be why dmrt1 is commonly used as the key male pathway gene in vertebrates and even in some invertebrates. [ABSTRACT FROM AUTHOR]