Gametogenesis is essential for the propagation of all sexually reproducing organisms and consists of halving the chromosome number through meiosis, and the subsequent packaging of the haploid products into gametes (sperm and eggs in mammals). Meiosis and gamete formation must be tightly coupled to ensure the formation of viable progeny; perturbations result in infertility, inviability and birth defects. Not surprisingly, a large number of signaling molecules participate in precisely regulating this cellular differentiation program. In the yeast Saccharomyces cerevisiae, sexual reproduction occurs via sporulation and is similar in many respects to gametogenesis in mammals. We have shown that the conserved signaling molecules Phospholipase D (PLO) and the Ste2O-like kinase, Sps1 are essential for yeast sporulation, but their precise roles in this process are largely unknown.We propose to continue to exploit the genetics of yeast to elucidate the signaling pathways involved in regulating the cellular differentiation program of sporulation. We will analyze the role of PLO and Sps1 using a three-pronged approach: 1) we wilt investigate the specific requirement for PLO-generated lipids in sporulation. 2) We will elucidate the function of a developmentally regulated Art-GAP and determine if it mediates PLO pathway function. 3) We will examine the relationship between PLD and Sps1 and identify additional components of the Sps1 signaling pathway. Taken together, our studies will provide a framework for understanding how cell signaling events are coordinated to ensure the formation of viable progeny. Given the extensive degree of evolutionary conservation between these molecules, it is likely that an understanding of the function of PLD and Sps1 in yeast wilt provide general insights into the role of orthologous molecules in humans and the consequences of their altered regulation in infertility, birth defects and disease.
