Regulation of the ERK signalling pathway in the developing mouse blastocyst

Development. 2019 Jul 25;146(14):dev177139. doi: 10.1242/dev.177139.

Abstract

Activation of the ERK signalling pathway is essential for the differentiation of the inner cell mass (ICM) during mouse preimplantation development. We show here that ERK phosphorylation occurs in ICM precursor cells, in differentiated primitive endoderm (PrE) cells as well as in the mature, formative state epiblast (Epi). We further show that DUSP4 and ETV5, factors often involved in negative-feedback loops of the FGF pathway, are differently regulated. Whereas DUSP4 presence clearly depends on ERK phosphorylation in PrE cells, ETV5 localises mainly to Epi cells. Unexpectedly, ETV5 accumulation does not depend on direct activation by ERK but requires NANOG activity. Indeed ETV5, like Fgf4 expression, is not present in Nanog mutant embryos. Our results lead us to propose that in pluripotent early Epi cells, NANOG induces the expression of both Fgf4 and Etv5 to enable the differentiation of neighbouring cells into the PrE while protecting the Epi identity from autocrine signalling.

Keywords: Blastocyst; Cell differentiation; Mouse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blastocyst / metabolism*
  • Blastocyst Inner Cell Mass / cytology
  • Blastocyst Inner Cell Mass / physiology
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Embryo, Mammalian
  • Embryonic Development / genetics*
  • Extracellular Signal-Regulated MAP Kinases / genetics*
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Fibroblast Growth Factor 4 / genetics
  • Fibroblast Growth Factor 4 / metabolism
  • Gene Expression Regulation, Developmental
  • Gene Expression Regulation, Enzymologic
  • MAP Kinase Signaling System* / genetics
  • Mice
  • Mice, Inbred ICR
  • Mice, Transgenic
  • Nanog Homeobox Protein / genetics
  • Nanog Homeobox Protein / metabolism
  • Protein Tyrosine Phosphatases / physiology
  • Signal Transduction / physiology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • DNA-Binding Proteins
  • Etv5 protein, mouse
  • Fgf4 protein, mouse
  • Fibroblast Growth Factor 4
  • Nanog Homeobox Protein
  • Nanog protein, mouse
  • Transcription Factors
  • Extracellular Signal-Regulated MAP Kinases
  • MKP2 protein, mouse
  • Protein Tyrosine Phosphatases