The precise regulation of germ cell fates (sperm or oocyte) lies at the heart of reproduction and fertility. The nematode Caenorhabditis elegans hermaphrodites produce a discrete number of sperm during larval development and then switch to produce oocyte during adulthood. A number of positive (e.g., fbf genes) and negative (e.g., gld-3) regulators are important for this switch. Here, we found that aberrant activation of MPK-1 (an ERK homolog) by removal of both fbf-1 and lip-1 partially inhibits sperm-oocyte switch, resulting in Mog (masculinization of germline) sterility. The fbf-1 gene encodes a conserved PUF (Pumilio and FBF) RNA-binding protein and the lip-1 gene encodes an MPK-1/ERK phosphatase. Notably, inhibition of MPK-1/ERK signaling by either genetic mutation or chemical inhibition reprograms the germ cell fate and thus helps in regaining the fertility. We also found that fbf-1; lip-1 Mog sterility was enhanced by the depletion of G2/M cell cycle regulators, including CYB-3/Cyclin B, CDK-1/CDK1, and CDC-25.1/CDC25. Markedly, cdc-25.1 mRNA is a direct target of FBF-1. These results suggest that FBF-1 and LIP-1 may promote sperm-oocyte switch by activating MPK-1/ERK signaling and G2/M cell cycle progression.M.S
