Genetic control of cell fate specification in Caenorhabditis elegans germline.

Abstract

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.