How maternal factors in oocytes initiate zygotic genome activation (ZGA) remains elusive in mammals, partly due to the challenge of de novo identification of key factors using scarce materials. The 2-cell (2C) embryo like cells has been widely used as an in vitro model to understand mouse ZGA and totipotency given its expression of a group of 2C embryo-specific genes and its simplicity for genetic manipulation. Recent studies indicate that DPPA2 and DPPA4 are required for establishing the 2C-like state in mouse embryonic stem cells (ESCs) in a DUX-dependent manner. These results suggest that DPPA2 and DPPA4 are essential maternal factors that regulate Dux and ZGA in embryos. By analyzing maternal knockout and maternal-zygotic knockout embryos, we unexpectedly found that DPPA2 and DPPA4 are dispensable for Dux activation, ZGA, and preimplantation development. Our study suggests that 2C-like cells do not fully recapitulate 2-cell embryos in terms of 2C-gene regulation and cautions should be taken when studying ZGA and totipotency using 2C-like cells as the model system.
DPPA2 and DPPA4 are dispensable for mouse zygotic genome activation and preimplantation development
Present address: The Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139, USA
- Award Group:
- Funder(s): Howard Hughes Medical Institute
- Award Id(s): Yi Zhang
- Funder(s):
- Award Group:
- Funder(s): Eunice Kennedy Shriver National Institute of Child Health and Human Development
- Award Id(s): R01HD092465
- Funder(s):
- Award Group:
- Funder(s): Eunice Kennedy Shriver National Institute of Child Health and Human Development
- Award Id(s): K99HD104902
- Funder(s):
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Zhiyuan Chen, Zhenfei Xie, Yi Zhang; DPPA2 and DPPA4 are dispensable for mouse zygotic genome activation and preimplantation development. Development 2021; dev.200178. doi: https://doi.org/10.1242/dev.200178
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