<i>foxl3</i>, a sexual switch in germ cells, initiates two independent molecular pathways for commitment to oogenesis in medaka.

Abstract

Germ cells have the ability to differentiate into eggs and sperm and must determine their sexual fate. In vertebrates, the mechanism of commitment to oogenesis following the sexual fate decision in germ cells remains unknown. <i>Forkhead-box protein L3</i> (<i>foxl3</i>) is a switch gene involved in the germline sexual fate decision in the teleost fish medaka (<i>Oryzias latipes</i>). Here, we show that <i>foxl3</i> organizes two independent pathways of oogenesis regulated by <i>REC8 meiotic recombination protein a</i> (<i>rec8a</i>), a cohesin component, and <i>F-box protein</i> (FBP<i>) 47</i> (<i>fbxo47</i>), a subunit of E3 ubiquitin ligase. In mutants of either gene, germ cells failed to undergo oogenesis but developed normally into sperm in testes. Disruption of <i>rec8a</i> resulted in arrest at a meiotic pachytenelike stage specifically in females, revealing a sexual difference in meiotic progression. Analyses of <i>fbxo47</i> mutants showed that this gene regulates transcription factors that facilitate folliculogenesis: <i>LIM homeobox 8</i> (<i>lhx8b</i>), <i>factor in the germline</i> α (<i>figla</i>), and <i>newborn ovary homeobox</i> (<i>nobox</i>). Interestingly, we found that the <i>fbxo47</i> pathway ensures that germ cells do not deviate from an oogenic pathway until they reach diplotene stage. The mutant phenotypes together with the timing of their expression imply that germline feminization is established during early meiotic prophase I.