Although fertilization is the most fundamental event of early development, biologists are only beginning to unravel the mechanisms responsible for signaling the completion of meiosis, cell division (cleavage), synthesis of embryonic proteins, and prevention of multiple sperm penetration by regulated secretion. Our research is aimed at discovering the normal signaling pathways activating these critical events, when the egg develops the biochemical machinery driving these pathways, and the molecular causes of human in vitro fertilization failure. We are particularly interested in determining how specific patterns of intracellular calcium release in the fertilized egg regulate the activity of important cell cycle kinases (CaMKII, MPF, and MAPK), expression of new proteins, and secretion. Such studies will determine how calcium signals are read out by specific proteins which in turn initiate the development of the embryo. These studies have implications for evaluating new clinical methods of fertilization and egg activation for animal cloning to produce therapeutic proteins. In addition, this mouse work has lead to studies of unfertilized eggs in human IVF procedures, indicating 2 classes of defective eggs: Those that are activation incompetent and those that prematurely activate, preventing fertilization.