Areas of Interest
Early embryonic development in mammals is highly error-prone, resulting in incidences of aneuploidies which are known to occur quite frequently in pre-implantation embryos. The high frequency of embryos with an abnormal number of chromosomes during early stages of development is a major driver for early-stage miscarriages. Defects in the function of specialized regions of chromosomes called centromeres represent a major cause of aneuploidy. This is because centromeres serve as the point of attachment for kinetochore proteins to chromosomes, which are proteins that are required for proper chromosome segregation during cell division. The recruitment of kinetochore proteins to centromeres is mediated by interactions with the centromere-specific histone H3 variant, CENP-A. Thus, CENP-A containing nucleosomes epigenetically define centromeric regions of chromosomes. Quantitative maintenance of CENP-A nucleosomes specifically at centromeres is known to be important for proper chromosome segregation as both depletion and overexpression of CENP-A in somatic cells has previously been shown to result in mitotic defects, such as aneuploidy. These observations suggest that impaired regulation of CENP-A dynamics in the early embryo could be contributing to the high rate of aneuploidy observed in early mammalian development. Therefore, I am interested in investigating the molecular mechanisms regulating CENP-A dynamics in early mouse embryos to understand how these processes promote faithful chromosome segregation during early stages of development.