Sequential, Divergent, and Cooperative Requirements of Foxl2a and Foxl2b in Ovary Development and Maintenance of Zebrafish

is essential for mammalian ovary maintenance. Although sexually dimorphic expression of was observed in many teleosts, its role and regulative mechanism in fish remained largely unclear. In this study, we first identified two transcript variants of and its homologous gene in zebrafish, and revealed their specific expression in follicular layer cells in a sequential and divergent fashion during ovary differentiation, maturation, and maintenance. Then, homozygous mutants ( ) and mutants ( ) were constructed and detailed comparisons, such as sex ratio, gonadal histological structure, transcriptome profiling, and dynamic expression of gonadal development-related genes, were carried out. Initial ovarian differentiation and oocyte development occur normally both in and mutants, but and disruptions result in premature ovarian failure and partial sex reversal, respectively, in adult females. In female mutants, / signaling was upregulated at 150 days postfertilization (dpf) and subsequently oocyte apoptosis was triggered after 180 dpf. In contrast, expression was greater at 105 dpf and increased several 100-fold in mutated ovaries at 270 dpf, along with other testis-related genes. Finally, homozygous / double mutants were constructed in which complete sex reversal occurs early and testis-differentiation genes robustly increase at 60 dpf. Given mutual compensation between and in and mutants, we proposed a model in which and cooperate to regulate zebrafish ovary development and maintenance, with potentially having a dominant role in preventing the ovary from differentiating as testis, as compared to .