The Role of 14-3-3 Proteins in Oogenesis and Early Development

点击翻译按钮获取中文摘要

Project Summary/Abstract The regulation of mammalian oocyte maturation is central to the formation of mature eggs that can be fertilized and develop into viable embryos. Oocyte maturation includes division of the nuclear material through meiosis to form a haploid egg cell, as well as changes in cell structure and signaling pathways that permit activation of the egg by sperm at fertilization and subsequent development. The collection of immature oocytes in human assisted reproduction clinics remains common, and greater understanding is needed to ensure the availability of mature eggs in clinical settings. Moreover, abnormalities of the spindle apparatus during meiosis could be associated with incidences of aneuploidy. The objective of this proposal is to provide insight into the basic cellular mechanisms that could later be applied to both animal and human reproduction. The cellular pathways that guide oocyte maturation and meiotic spindle function during meiosis are complex and are dependent on intricate interactions among and between protein assemblages. One approach to studying this process is to examine the role of key adaptor and regulatory proteins and their interaction with known signaling factors, particularly the kinases and phosphatases that we know to be central to meiosis. The 14-3-3 (YWHA) proteins in somatic cells are vital regulators in a number of signal transduction pathways, cell cycle control, protein trafficking, apoptosis, and aspects of embryonic development. There is evidence to indicate that the 14-3-3 proteins are also critical regulators in meiosis and in the formation of meiotic spindles. The overall goal of this project is to delineate the functions of 14-3-3 proteins in oocyte maturation. Focusing on filling in some of the gaps in our understanding of mammalian oocyte maturation and early development, in Aims 1 and 2, the role of 14-3-3 will be assessed by examining each of the seven 14-3-3 isoforms as they form dimers and detailing the protein complexes they are involved in. Oocyte-specific 14-3-3 knockout mouse models will be used in Aim 3 to test the hypothesis that 14-3-3 proteins contribute to the regulation of meiosis and spindle formation. The combination of identifying interacting proteins and determining the function of such interactions will enhance our understanding of mammalian oogenesis.