Posttranscriptional regulation of gene expression, typically effected by RNA-binding proteins, microRNAs (miRNAs), and translation initiation factors, is essential for normal germ cell function. Numerous miRNAs have been detected in the germline; however, the functions of specific miRNAs remain largely unknown. Functions of miRNAs have been difficult to determine as miRNAs often modestly repress target mRNAs and are suggested to sculpt or fine tune gene expression to allow for the robust expression of cell fates. In Caenorhabditis elegans hermaphrodites, cell fate decisions are made for germline sex determination during larval development when sperm are generated in a short window before the switch to oocyte production. Here, analysis of newly generated mir-44 family mutants has identified a family of miRNAs that modulate the germline sex determination pathway in C. elegans. Mutants with the loss of mir-44 and mir-45 produce fewer sperm, showing both a delay in the specification and formation of sperm as well as an early termination of sperm specification accompanied by a premature switch to oocyte production. mir-44 and mir-45 are necessary for the normal period of fog-1 expression in larval development. Through genetic analysis, we find that mir-44 and mir-45 may act upstream of fbf-1 and fem-3 to promote sperm specification. Our research indicates that the mir-44 family promotes sperm cell fate specification during larval development and identifies an additional posttranscriptional regulator of the germline sex determination pathway.

Complementary forward and reverse genetic approaches in several model systems have resulted in a recent burst of fertilization gene discovery. The number of genetically validated gamete surface molecules have more than doubled in the last few years. All the genetically validated sperm fertilization genes encode transmembrane or secreted molecules. Curiously, the discovery of genes that encode oocyte molecules have fallen behind that of sperm genes. This review discusses potential experimental biases and inherent biological reasons that could slow egg fertilization gene discovery. Finally, we shed light on current strategies to identify genes that may result in further identification of egg fertilization genes.

No abstract

Infertility and development of contraceptive methods have profound societal affects; however, the genetic mechanisms underlying this are still largely unknown. Here, we describe how using the small worm Caenorhabditis elegans has helped us to discover the genes involved in these processes. Nobel Laureate Sydney Brenner established the nematode worm C. elegans as a genetic model system with a powerful ability to discover genes in many biological pathways through mutagenesis. In this tradition, many labs have been using the substantial genetic tools established by Brenner and the ‘worm’ research community to discover genes required for uniting sperm and egg. Our understanding of the molecular underpinnings of the fertilization synapse between sperm and egg rivals that of any organism. Genes have been discovered in worms that share homology and mutant phenotypes with mammals. We provide an overview of the state of our understanding of fertilization in worms as well as exciting future directions and challenges.