The Oocyte - to - Embryo Transition : Regulation of Oocyte Maturation and Egg Activation in Drosophila

In oogenesis, meiosis must be highly regulated to ensure that growth of the oocyte and chromosomal segregation are coordinated properly. To do this, meiosis arrests at two points to permit oocyte differentiation and coordination with fertilization. In Drosophila, the first arrest in prophase I is released by oocyte maturation, and the second arrest in metaphase I is released by egg activation. This thesis explores mechanisms controlling these two processes. First, the putative role of the Deadhead (DHD) thioredoxin in Drosophila female meiosis is examined. Possible roles that DHD may play in DNA replication, ROS/RNS redox pathways, and vitelline membrane crosslinking are explored. Furthermore, current research into the role of Ca 2 as a regulator of Drosophila egg activation is summarized. Recent studies have suggested that Sarah (Sra), a regulator of Calcineurin (CN), is required for egg activation and meiotic completion. A model for Sra/CN signaling is presented, highlighting the role of Ca2+ in Drosophila activation, and emphasizing aspects of meiotic activation conserved across species. Finally, proteins recovered from a large-scale proteomic screen undertaken by our lab are discussed. This screen identified proteins that increase or decrease significantly during the processes of maturation and activation through quantitative mass spectrometry. Pairwise comparison of protein levels between preand postmaturation oocytes (stage 10 vs. stage 14 oocytes) or preand postactivation eggs (stage 14 vs. unfertilized eggs) identified candidate proteins upand downregulated during one or both of these processes. These candidates include proteins involved in calcium binding and transport, the ubiquitination pathway, steroid biosynthesis and metabolism, and a gap junction protein. Additional characterization of these proteins may provide further insight into the regulation of Drosophila maturation and activation. Thesis Supervisor: Terry L. Orr-Weaver Title: Professor of Biology