Zebrafish Foxl2l functions in proliferating germ cells for female meiotic entry

Abstract Zebrafish sex differentiation is a complicated process and the detailed mechanism has not been fully understood. Here we characterized a transcription factor, Foxl2l, that participates in female oogenesis. We show that it is expressed specifically in proliferating germ cells in juvenile gonads and mature ovaries. We have used CRISPR-Cas9 to generate zebrafish deficient in foxl2l expression. Zebrafish with foxl2l -/- are all males, and this female-to-male sex reversal cannot be reversed by tp53 mutation, indicating this sex reversal is unrelated to cell death. We have generated transgenic fish expressing GFP under the control of foxl2l promoter to track the development of foxl2l + -germ cells, which failed to enter meiosis and were accumulated as cystic cells. Our RNA-seq analysis also showed the reduced expression of genes in meiosis and oogenesis among other affected pathways. All together, we show that zebrafish Foxl2l is a nuclear factor controlling the expression of meiotic and oogenic genes, and its deficiency leads to defective meiotic entry and the accumulation of premeiotic germ cells. Highlights Zebrafish foxl2l is expressed only in proliferating germ cells in juvenile gonads and mature ovaries. Foxl2l is a nuclear factor that promotes expression of genes involved in meiosis and oogenesis. Zebrafish depleted of foxl2l lack meiotic oocytes in juveniles and become all males in adults. Mutation of foxl2l leads to the accumulation of premeiotic germ cells.