Germline sexual fate is determined by the antagonistic action of dmrt1 and foxl3/foxl2 in tilapia

Germline sexual fate has long been believed to be determined by the somatic environment, but this idea is challenged by recent studies of foxl3 mutants in medaka. Here, we demonstrate that the sexual fate of tilapia germline is determined by the antagonistic interaction of dmrt1 and foxl3, which are transcriptionally repressed in male and female germ cells, respectively. Loss of dmrt1 rescued the germ cell sex reversal in foxl3(Delta)(7/Delta 7) XX fish, and loss of foxl3 partially rescued germ cell sex reversal but not somatic cell fate in dmrt1(Delta 5)(/Delta 5) XY fish. Interestingly, germ cells lost sexual plasticity in dmrt1(Delta 5)(/Delta 5 )XY and foxl3(Delta)(7/Delta 7) XX single mutants, as aromatase inhibitor (AI) and estrogen treatment failed to rescue the respective phenotypes. However, recovery of germ cell sexual plasticity was observed in dmrtl/foxl3 double mutants. Importantly, mutation of somatic cell-specific foxl2 resulted in testicular development in foxl3(Delta)(7/Delta 7) or dmrt1(Delta 5)(/Delta 5) mutants. Our findings demonstrate that sexual plasticity of germ cells relies on the presence of both dmrt1 and foxl3. The existence of dmrt1 and foxl3 allows environmental factors to influence the sex fate decision in vertebrates.

Automated summary

Recent studies challenge the long-standing belief that germline sexual fate is determined by the somatic environment, showing instead that in tilapia, the sexual fate of germline is determined by the antagonistic interaction of dmrt1 and foxl3. Our findings suggest that the sexual plasticity of germ cells relies on the presence of both dmrt1 and foxl3, allowing environmental factors to influence sex fate decision in vertebrates.