FGFR1 regulates trophectoderm development and facilitates blastocyst implantation

• Published in: Developmental biology Vol. 446; no. 1; pp. 94 - 101
• Main Authors: Kurowski, Agata, Molotkov, Andrei, Soriano, Philippe
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-02-2019
• Subjects: Animals; CDX2 Transcription Factor - genetics; CDX2 Transcription Factor - metabolism; Cell Differentiation - genetics; Cell Line; Cells, Cultured; Ectoderm - cytology; Embryo Implantation - genetics; Female; FGF; Gene Expression Regulation, Developmental; Mice; Mice, 129 Strain; Mice, Knockout; Pregnancy; Receptor, Fibroblast Growth Factor, Type 1 - genetics; Receptor, Fibroblast Growth Factor, Type 1 - metabolism; Receptor, Fibroblast Growth Factor, Type 2 - genetics; Receptor, Fibroblast Growth Factor, Type 2 - metabolism; Trophectoderm; Trophoblasts - cytology; Trophoblasts - metabolism; TS cells; Trophectoderm; FGF; TS cells
• ISSN: 0012-1606; 1095-564X
• DOI: 10.1016/j.ydbio.2018.12.008

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.
•Fgfr1-/- embryos fail to downregulate Cdx2 in the mural trophectoderm.•Fgfr1-/- trophectoderm cells exhibit abnormal apicobasal E-Cadherin polarity.•TSCs from Fgfr1-/- or Fgfr2-/- mutants, but not double mutants, can be isolated and maintained.•Fgfr1-/- TSCs fail to efficiently express TE differentiation markers upon differentiation.•Taken together, these results highlight the role for FGF signaling in trophectoderm development.