Epigenetic Reprogramming in the Murine Egg and Early Embryo.

Once ovulated, the terminally differentiated mammalian oocyte will die if it does not bind and fuse with a sperm. If fertilization occurs, however, maternal gene products orchestrate the transformation of the egg into a totipotent zygote within hours. My lab is investigating the role that novel, highly-abundant, and egg-restricted molecules play in this reprogramming process. Currently, we are focusing on one such gene product, peptidylarginine deiminase 6 (PADI6) which we have localized to a poorly characterized egg-restricted structure, the cytoplasmic lattices (CPLs). The CPLs, which occupy about twenty percent of the egg cytoplasm, have been described in the literature for over 40 years, yet their function remains poorly defined. Through use of mouse knockout models, we have discovered that PADI6 is required for CPL formation during oogenesis, thus suggesting that PADI6 is an integral component of the CPL complex. Further, we have found that PADI6 is required for development beyond the two-cell stage, thus indicating that PADI6 represents one of a handful of known mammalian factors that are produced by the mother and then endowed to the embryo to help manage the early stages development. Currently, we are exploring the mechanisms by which PADI6 and the CPLs regulate embryonic reprogramming and, more specifically, are investigating whether PADI6 plays a direct role in the establishment of totipotency during embryonic genome activation at the two-cell stage via cytoplasmic-to-nuclear signaling events.