Distinct Requirements for FGFR1 and FGFR2 in Primitive Endoderm Development and Exit from Pluripotency

Dev Cell. 2017 Jun 5;41(5):511-526.e4. doi: 10.1016/j.devcel.2017.05.004. Epub 2017 May 25.

Abstract

Activation of the FGF signaling pathway during preimplantation development of the mouse embryo is known to be essential for differentiation of the inner cell mass and the formation of the primitive endoderm (PrE). We now show using fluorescent reporter knockin lines that Fgfr1 is expressed in all cell populations of the blastocyst, while Fgfr2 expression becomes restricted to extraembryonic lineages, including the PrE. We further show that loss of both receptors prevents the development of the PrE and demonstrate that FGFR1 plays a more prominent role in this process than FGFR2. Finally, we document an essential role for FGFRs in embryonic stem cell (ESC) differentiation, with FGFR1 again having a greater influence than FGFR2 in ESC exit from the pluripotent state. Collectively, these results identify mechanisms through which FGF signaling regulates inner cell mass lineage restriction and cell commitment during preimplantation development.

Keywords: FGF; epiblast; pluripotency; primitive endoderm; signaling.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Blastocyst Inner Cell Mass / cytology
  • Blastocyst Inner Cell Mass / metabolism
  • Cell Differentiation
  • Cell Lineage
  • Cells, Cultured
  • Embryo, Mammalian / cytology*
  • Embryo, Mammalian / metabolism
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / metabolism
  • Endoderm / cytology*
  • Endoderm / metabolism
  • Female
  • Fibroblast Growth Factor 4 / metabolism*
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptor, Fibroblast Growth Factor, Type 1 / physiology*
  • Receptor, Fibroblast Growth Factor, Type 2 / physiology*
  • Signal Transduction

Substances

  • Fgf4 protein, mouse
  • Fibroblast Growth Factor 4
  • Fgfr1 protein, mouse
  • Fgfr2 protein, mouse
  • Receptor, Fibroblast Growth Factor, Type 1
  • Receptor, Fibroblast Growth Factor, Type 2