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.
Original language | English |
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Pages (from-to) | 94-101 |
Number of pages | 8 |
Journal | Developmental Biology |
Volume | 446 |
Issue number | 1 |
DOIs | |
State | Published - 1 Feb 2019 |
Keywords
- FGF
- TS cells
- Trophectoderm