During sexual reproduction in most animals, oocytes arrest in meiotic prophase and resume meiosis (meiotic maturation) in response to sperm or somatic cell signals. Despite progress in delineating mitogen-activated protein kinase (MAPK) and CDK/cyclin activation pathways involved in meiotic maturation, it is less clear how these pathways are regulated at the cell surface. TheCaenorhabditis elegansmajor sperm protein (MSP) signals oocytes, which are arrested in meiotic prophase, to resume meiosis and ovulate. We used DNA microarray data and an in situ binding assay to identify the VAB-1 Eph receptor protein–tyrosine kinase as an MSP receptor. We show that VAB-1 and a somatic gonadal sheath cell-dependent pathway, defined by the CEH-18 POU-class homeoprotein, negatively regulate meiotic maturation and MAPK activation. MSP antagonizes these inhibitory signaling circuits, in part by binding VAB-1 on oocytes and sheath cells. Our results define a sperm-sensing control mechanism that inhibits oocyte maturation, MAPK activation, and ovulation when sperm are unavailable for fertilization. MSP-domain proteins are found in diverse animal taxa, where they may regulate contact-dependent Eph receptor signaling pathways.

During sexual reproduction in many species, sperm and oocyte secrete diffusible signaling molecules to help orchestrate the biological symphony of fertilization. In theCaenorhabditis elegansgonad, bidirectional signaling between sperm and oocyte is important for guiding sperm to the fertilization site and inducing oocyte maturation. The molecular mechanisms that regulate sperm guidance and oocyte maturation are being delineated. Unexpectedly, these mechanisms are providing insight into human diseases, such as amyotrophic lateral sclerosis, spinal muscular atrophy, and cancer. Here we review sperm and oocyte communication inC. elegansand discuss relationships to human disorders. Developmental Dynamics 239:1265–1281, 2010.