Developmental Cell
Volume 41, Issue 5, 5 June 2017, Pages 496-510.e5
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Article
Lineage Establishment and Progression within the Inner Cell Mass of the Mouse Blastocyst Requires FGFR1 and FGFR2

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Highlights

  • FGF4 drives EPI versus PrE specification within the ICM of the mouse blastocyst

  • FGF4 signals to two FGF receptors: a pan-ICM FGFR1 and PrE-biased FGFR2

  • FGFR1 is the key receptor regulating fate establishment and progression in the ICM

  • Differential MAPK/ERK activity ensures lineage divergence from a single FGF ligand

Summary

Fibroblast growth factor 4 (FGF4) is the key signal driving specification of primitive endoderm (PrE) versus pluripotent epiblast (EPI) within the inner cell mass (ICM) of the mouse blastocyst. To gain insight into the receptor(s) responding to FGF4 within ICM cells, we combined single-cell-resolution quantitative imaging with single-cell transcriptomics of wild-type and Fgf receptor (Fgfr) mutant embryos. Despite the PrE-specific expression of FGFR2, it is FGFR1, expressed by all ICM cells, that is critical for establishment of a PrE identity. Signaling through FGFR1 is also required to constrain levels of the pluripotency-associated factor NANOG in EPI cells. However, the activity of both receptors is required for lineage establishment within the ICM. Gene expression profiling of 534 single ICM cells identified distinct downstream targets associated with each receptor. These data lead us to propose a model whereby unique and additive activities of FGFR1 and FGFR2 within the ICM coordinate establishment of two distinct lineages.

Keywords

blastocyst
inner cell mass
epiblast
primitive endoderm
pluripotency
FGF
GATA6
NANOG
quantitative image analysis
single-cell transcriptomics

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Present address: Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305, USA

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