FGFR1 regulates trophectoderm development and facilitates blastocyst implantation

FGF signaling plays important roles in many aspects of mammalian development. Fgfr1(-/-) and Fgfr1(-/-) Fgfr2(-/-) 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 Fgfr1(-/-) Fgfr2(-/-) 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 Fgfr1(-/-) Fgfr2(-/-) 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.