The Birth of Embryonic Pluripotency

Philos Trans R Soc Lond B Biol Sci. 2014 Dec 5;369(1657):20130541. doi: 10.1098/rstb.2013.0541.


Formation of a eutherian mammal requires concurrent establishment of embryonic and extraembryonic lineages. The functions of the trophectoderm and primitive endoderm are to enable implantation in the maternal uterus, axis specification and delivery of nutrients. The pluripotent epiblast represents the founding cell population of the embryo proper, which is protected from ectopic and premature differentiation until it is required to respond to inductive cues to form the fetus. While positional information plays a major role in specifying the trophoblast lineage, segregation of primitive endoderm from epiblast depends upon gradual acquisition of transcriptional identity, directed but not initiated by fibroblast growth factor (FGF) signalling. Following early cleavage divisions and formation of the blastocyst, cells of the inner cell mass lose totipotency. Developing epiblast cells transiently attain the state of naive pluripotency and competence to self-renew in vitro as embryonic stem cells and in vivo by means of diapause. This property is lost after implantation as the epiblast epithelializes and becomes primed in preparation for gastrulation and subsequent organogenesis.

Keywords: cleavage; epiblast; pluripotency; primitive endoderm; totipotency; trophoblast.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Differentiation / physiology*
  • Cell Lineage / physiology*
  • Embryo, Mammalian / cytology*
  • Embryo, Mammalian / embryology*
  • Embryonic Development / physiology*
  • Germ Layers / embryology*
  • Mice
  • Models, Biological
  • Protein-Serine-Threonine Kinases / metabolism
  • Signal Transduction / physiology
  • Totipotent Stem Cells / physiology*


  • Hippo protein, mouse
  • Protein-Serine-Threonine Kinases