The goal of this project is to understand how a mammalian organism initiates its multicellular development by completing its very first asymmetric cell divisions (ACD) - during meiotic maturation and fertilization of the oocyte. Meiotic ACD not only is critically important for successful fertilization and full developmental potential of the zygote, but also offers unique and fascinating insights into the mechanism of self-organization, a most fundamental property of biological systems. Recent studies from our lab and others using mouse oocytes as the model system have begun to unravel dynamic and bi-directional interplays between the chromosomes and the actin cytoskeleton in setting up oocyte cell polarity for ACD and potentially also for future embryonic development. In the proposed research, we plan to build on these exciting recent findings to answer three mechanistic questions: 1) how actin dynamics drive oocyte symmetry breaking (Aim1); 2) how the nuclear genome directly signals morphological reorganization on the cellular level (Aim2); and 3) how an unusual mechanism of dynamic force production patterns a large cell (the oocyte) and potentially impacts organelle segregation and early embryonic development (Aim3). To answer these questions, we will employ a highly innovative approach that entails a full integration of molecular genetic methods with cutting-edge imaging technologies, biophysical tools and mathematical analysis. Because clinical evidence suggests that defects in the polarized organization of mature oocytes are associated with aging-related infertility, our study not only has the potential for novel intellectual contribution to the understanding of self-organization in cellular systems but may also provide the basis for future development of new methods that help improve human fertility and prevent birth defects.
Our research is designed to use mouse oocytes as the experimental model to unravel the key molecular machineries required for asymmetric meiotic cell division. The knowledge gained can form the basis for the development of new therapeutic methods to improve human fertility and prevent birth defects.
