Cell-Cycle-Dependent ERK Signaling Dynamics Direct Fate Specification in the Mammalian Preimplantation Embryo

Dev Cell. 2020 Nov 9;55(3):328-340.e5. doi: 10.1016/j.devcel.2020.09.013. Epub 2020 Oct 21.


Despite the noisy nature of single cells, multicellular organisms robustly generate different cell types from one zygote. This process involves dynamic cross regulation between signaling and gene expression that is difficult to capture with fixed-cell approaches. To study signaling dynamics and fate specification during preimplantation development, we generated a transgenic mouse expressing the ERK kinase translocation reporter and measured ERK activity in single cells of live embryos. Our results show primarily active ERK in both the inner cell mass and trophectoderm cells due to fibroblast growth factor (FGF) signaling. Strikingly, a subset of mitotic events results in a short pulse of ERK inactivity in both daughter cells that correlates with elevated endpoint NANOG levels. Moreover, endogenous tagging of Nanog in embryonic stem cells reveals that ERK inhibition promotes enhanced stabilization of NANOG protein after mitosis. Our data show that cell cycle, signaling, and differentiation are coordinated during preimplantation development.

Keywords: ERK; NANOG; blastocyst; cell cycle; embryonic stem cells; preimplantation development; signaling dynamics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Blastocyst / cytology*
  • Blastocyst / enzymology*
  • Cell Cycle*
  • Cell Lineage*
  • Germ Layers / cytology
  • Humans
  • MAP Kinase Signaling System*
  • Mammals / embryology*
  • Mice
  • Mitosis
  • Models, Biological
  • Nanog Homeobox Protein / metabolism
  • Protein Stability
  • Reproducibility of Results


  • Nanog Homeobox Protein