Src-family tyrosine kinases participate in the regulation of mammalian oocyte maturation and zygotic development.

摘要

Mammalian oocytes engage in a remarkable series of cytoskeletal and cell cycle modifications that prepare the oocyte for the initiation and continuance of development. Multiple signaling pathways appear to operate during the process of oocyte maturation to ensure that the quality of the cytoplasm and genome will meet the standards required to initiate and complete development. In this thesis we have taken a systematic approach to understand the role of Src-family kinases (SFKs) during oocyte maturation, fertilization and early cleavage in the mouse. We first demonstrate that the SFK that controls the progression of meiosis at the first metaphase anaphase transition is most likely FYN (Chapter 2). This proposal is then supported by the demonstration that tyrosine kinases act upon discrete subcellular compartments that include the oocyte cortex and spindle poles in a way that is spatially and temporally distinguishable from the targets of ser/thr kinases (Chapter 3). Moreover, this work reinforces the specific role of FYN at these sites within mouse oocytes using mice null for this SFK. Finally, in Chapter 4 we show that the functions of SFKs that drive completion of the meiotic cell cycle extend to and through the first embryonic cell cycle after fertilization. Thus, previously unanticipated functions for SFKs have been identified for the first time that mediate the spatial and temporal remodeling of cytoskeleton and cell cycle during oocyte maturation and early development. These findings will have an immediate impact on the field of human assisted reproductive technologies (ARTs) as this pathway has been completely overlooked up to now.