Anti-FBXO47 (aa 401-450) polyclonal antibody

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. Forkhead-box protein L3 (foxl3) is a switch gene involved in the germline sexual fate decision in the teleost fish medaka (Oryzias latipes). Here, we show that foxl3 organizes two independent pathways of oogenesis regulated by REC8 meiotic recombination protein a (rec8a), a cohesin component, and F-box protein (FBP) 47 (fbxo47), 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 rec8a resulted in arrest at a meiotic pachytenelike stage specifically in females, revealing a sexual difference in meiotic progression. Analyses of fbxo47 mutants showed that this gene regulates transcription factors that facilitate folliculogenesis: LIM homeobox 8 (lhx8b), factor in the germline a (figla), and newborn ovary homeobox (nobox). Interestingly, we found that the fbxo47 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.

A novel gene, prom-1, was isolated in a screen for Caenorhabditis elegans mutants with increased apoptosis in the germline. prom-1 encodes an F-box protein with limited homology to the putative human tumor suppressor FBXO47. Mutations in the prom-1 locus cause a strong reduction in bivalent formation, which results in increased embryonic lethality and a Him phenotype. Furthermore, retarded and asynchronous nuclear reorganization as well as reduced homologous synapsis occur during meiotic prophase. Accumulation of recombination protein RAD-51 in meiotic nuclei suggests disturbed repair of double-stranded DNA breaks. Nuclei in prom-1 mutant gonads timely complete mitotic proliferation and premeiotic replication, but they undergo prolonged delay upon meiotic entry. We, therefore, propose that prom-1 regulates the timely progression through meiotic prophase I and that in its absence the recognition of homologous chromosomes is strongly impaired.