FGFR1 regulates trophectoderm development and facilitates blastocyst implantation.

FGF signaling plays important roles in many aspects of mammalian development. Fgfr1 and Fgfr1Fgfr2 mouse embryos on a 129S4 co-isogenic background fail to survive past the peri-implantation stage, whereas Fgfr2 embryos die at midgestation and show defects in limb and placental development. To investigate the basis for the Fgfr1 and Fgfr1Fgfr2 peri-implantation lethality, we examined the role of FGFR1 and FGFR2 in trophectoderm (TE) development. In vivo, Fgfr1 TE cells failed to downregulate CDX2 in the mural compartment and exhibited abnormal apicobasal E-Cadherin polarity. In vitro, we were able to derive mutant trophoblast stem cells (TSCs) from Fgfr1 or Fgfr2 single mutant, but not from Fgfr1Fgfr2 double mutant blastocysts. Fgfr1 TSCs however failed to efficiently upregulate TE differentiation markers upon differentiation. These results suggest that while the TE is specified in Fgfr1 mutants, its differentiation abilities are compromised leading to defects at implantation.