FGFR1 regulates trophectoderm development and facilitates blastocyst implantation

Abstract 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.