Cytoskeletal Regulation of Cortical Mechanics in Mammalian Eggs

The cell cortex, which underlies the plasma membrane, performs the essential function of regulating the cell’s shape and mechanics. Cellular mechanical properties such as cortical tension have been characterized with the studies of mitosis in invertebrate zygotes starting in the early 20th century. Multiple types of mitotic cells have since been investigated, showing that progression through cytokinesis is coordinated by the crosstalk among the mechanics, cell shape, and mediating signals from cytoskeletal networks during mitosis. Mechanical features of mammalian female meiosis, however, are only beginning to be elucidated. The work in this thesis presents some of the first quantitative characterization of cortical mechanics of mammalian oocytes. Using micropipette aspiration, we show that the cortical tension of mouse oocytes changes dramatically during meiotic maturation from prophase I to metaphase II. Our data further demonstrate that oocyte tension is mediated by key proteins associated with the cortical cytoskeleton, including actin, myosin-II, and actin-to-membrane crosslinking proteins known as Ezrin-Radixin-Moesin (ERMs). Building on this study of the structural basis of oocyte mechanics, we show that p21-activated kinases (PAKs) contribute to oocyte mechanics, cell shape, and the localizations of several cortical cytoskeletal proteins. These findings are significant to reproductive success, since errors in divisions could result in aneuploidy, leading to abnormal embryonic development and congenital birth defects. Abnormal polar body emission has also been associated with female infertility or subfertility. Therefore, expanding our understanding of the mechanics of female meiosis carries both scientific and clinical implications