The zebrafish dmrt family genes have cooperative and antagonistic roles in sex determination and oogenesis

Abstract

The double-sex and mab3 related transcription factor (dmrt) gene family has conserved roles in sex determination and gonad development across metazoans. In zebrafish, dmrt1 was previously shown to function in male sex-determination and testes development. To gain a broader knowledge of this gene family in sexual development, we investigated potential roles of all zebrafish dmrt family genes in sex-determination and gonad development using mutant analysis. The dmrt2a and dmrt5 mutants conferred lethality prior to sex differentiation, whereas dmrt2b and dmrt3 mutants were viable and fertile. Dmrt2b mutants had normal sex ratios while dmrt3 showed slightly skewed sex ratios in some experiments, indicating that dmrt3 has a minor role in sex-determination. We report a previously unknown role for dmrt1 in ovary development. Although dmrt1 mutant females were fertile, oogenesis did not progress normally, as evident from abnormal proportions of differently-staged oocytes within mutant ovaries. We also asked if dmrt1 mutant phenotypes could be modified by loss of another dmrt family member. Analysis of dmrt1;dmrt2a mutants was possible as these double mutants were sub-viable, showing a partial rescue of the dmrt2a lethality in the dmrt1 mutant background. The dmrt1;dmrt2a mutants had less severe female bias than dmrt1 mutants suggesting that dmrt2a acts antagonistically to dmrt1 in sex determination. Double mutants of dmrt1 with either dmrt2a or dmrt3 had more severe oogenesis defects than dmrt1 mutants and had either sub-fertility with reduced fecundity or failed to breed, respectively. This study reveals previously unknown roles of zebrafish dmrt1, dmrt2a, and dmrt3 in oogenesis.