The CDC14B Phosphatase Is a Negative Regulator of Pre-Implantation Embryonic Development in Mouse.

Abstract

Following fertilization, the transition from a highly differentiated oocyte to totipotent 2-cell blastomeres requires two unique mitotic cell cycles. The first cell cycle is characterized by a prolonged G1 phase and DNA replication (S phase) that occurs separately in the female and male pronuclei. During the second cell cycle, the G2 phase is prolonged and occurs concurrently with zygotic genome activation, which is essential for progression past the 2-cell embryonic stage. CDC14B, a dual specificity phosphatase that counteracts cyclin dependent kinase 1 (CDK1) action, regulates mitosis in somatic cells and prevents premature meiotic resumption in mouse oocytes. It is not known if CDC14B plays a role during the unique mitotic cell cycles during preimplantation development. We demonstrate that CDC14B is present in preimplantation mouse embryos and that it localizes to mitotic centrosomes and spindles. Over-expression of CDC14B in 1-cell embryos prevents development to the blastocyst stage as 40% and 60% of the embryos arrest at the 1 and 2-cell stages, respectively. The embryos that arrest at the 1-cell stage contain reduced CDK1 activity, suggesting that this block is due to a cell cycle defect. Notably, the embryos that arrest at the 2-cell stage fail to activate the zygotic genome despite having normal levels of CDK1 activity. This function is likely specific to embryos because over-expression of CDC14B in meiotically incompetent oocytes that are transcriptionally active does not repress global transcription. These data suggest that CDC14B is a negative regulator of the 1-to-2-cell transition and of zygotic genome activation in mouse embryogenesis. K.S. was supported by HD055822 and M.G.B. was supported by 5D43TW000671. This research was supported by a grant from the NIH (HD22681) to R.M.S. (poster)