| The first cell fate decision in the mouse embryo occurs when the daughters of equipotential blastomeres make the decision to become either trophectoderm (TE), or inner cell mass (ICM). It is unclear both how factors thought to crucial for the TE and ICM fates interact within an intact embryo, and whether each of the early blastomeres in the embryo possesses an equal tendency to contribute to TE and ICM.;We first used an immunofluorescence timecourse to determine how TE- and ICM-specific factors interact within the embryo. Our observations suggested that downregulation of Oct4 and Nanog is not necessary for proper function of the TE. We next used an inducible system to drive ectopic expression of either Oct4 or Nanog in the TE, and found that ectopic Oct4 is able to perturb expression of Nanog, but not Cdx2 and Sox2. These embryos also appeared capable of successful development to adulthood. Our results suggested that either Cdx2 is sufficient to disrupt pluripotency, or that all 3 pluripotency factors are needed to repress TE differentiation. To distinguish between these possibilities, we analyzed expression of Sox2, Nanog, and Oct4 in mESCs cultured with or without induced expression of Cdx2. We found that Cdx2 induction quickly represses Oct4, but not Sox2 or Nanog. We therefore propose a model where Cdx2 destabilizes the pluripotency network within the embryo by Oct4 repression only.;Assessment of blastomere equivalence in the early embryo has been hampered by the lack of a non-invasive lineage tracing method that can uniquely label individual cells. We generated mice that allow multicolor lineage tracing, allowing us to uniquely and indelibly label each blastomere. In a substantial fraction of embryos, we found biased contribution of blastomere daughters to either the TE or the ICM that seems to be maintained after implantation. This biased contribution did not seem to be explained through a similar bias in the contribution of these blastomeres to the embryonic and abembryonic parts of the blastocyst. It is possible that this bias arises through unequal tendency of individual blastomeres to undergo asymmetric cell divisions in the morula. |
