In most sexually reproducing animals, oocytes arrest in meiotic prophase and resume meiosis (meiotic maturation) in response to sperm or somatic cell signals. In humans, dysregulation of the meiotic process in females is a major cause of miscarriage, infertility, and chromosomal non-disjunction syndromes, such as Down's. To complement studies in vertebrates, we are using C. elegans as a model for studying the control of meiosis by intercellular signaling. Our studies demonstrate that the C. elegans major sperm protein (MSP), a cytoskeletal protein required for amoeboid motility of nematode sperm, has a second critical function as a hormone that promotes oocyte meiotic maturation. MSP signaling activates the conserved MAPK cascade in oocytes and results in diverse cellular responses including M-phase entry, cortical cytoskeletal rearrangement, histone H3 phosphorylation, and meiotic spindle assembly. Recent results suggest that MSP promotes M-phase entry and MAPK activation by antagonizing the function of the VAB-1 Eph receptor protein-tyrosine kinase and a somatic gonadal sheath cell-dependent pathway. Having defined the sperm-derived signal and a receptor that regulate meiotic maturation, we aim to characterize downstream molecular mechanisms necessary for oocyte maturation events, and to define the mechanism of MSP release from spermatids and spermatozoa. We will elucidate the function of the std-1 locus, which is defined by a semi-dominant mutation that interferes with normal oocyte meiotic maturation processes and results in non-disjunction of meiotic chromosomes. We will also determine whether MSP release from sperm is vesicle-mediate or involves the function of ABC transporters that are enriched in the male germ line. These experiments will provide insight into the regulation oocyte meiotic maturation by intercellular signaling and will illuminate fundamental cell biological mechanisms underlying animal reproduction.