The differential response to Fgf signalling in cells internalized at different times influences lineage segregation in preimplantation mouse embryos

Samantha A. Morris, Sarah J.L. Graham, Agnieszka Jedrusik, Magdalena Zernicka-Goetz

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

Lineage specification in the preimplantation mouse embryo is a regulative process. Thus, it has been difficult to ascertain whether segregation of the innercell- mass (ICM) into precursors of the pluripotent epiblast (EPI) and the differentiating primitive endoderm (PE) is random or influenced by developmental history. Here, our results lead to a unifying model for cell fate specification in which the time of internalization and the relative contribution of ICM cells generated by two waves of asymmetric divisions influence cell fate. We show that cells generated in the second wave express higher levels of Fgfr2 than those generated in the first, leading to ICM cells with varying Fgfr2 expression. To test whether such heterogeneity is enough to bias cell fate, we upregulate Fgfr2 and show it directs cells towards PE. Our results suggest that the strength f this bias is influenced by the number of cells generated in the first wave and, mostly likely, by the level of Fgf signalling in the ICM. Differences i the developmental potential of eight-cell- and 16-cell-stage outside blastomeres placed in the inside of chimaeric embryos further support this conclusion. These results unite previous findings demonstrating the importance of developmental history and Fgf signalling in determining cell fate.

Original languageEnglish
Article number130104
JournalOpen Biology
Volume3
Issue numberNOV
DOIs
StatePublished - Nov 20 2013
Externally publishedYes

Keywords

  • Bias
  • Cell lineage
  • Fgf signalling
  • Heterogeneity
  • Mouse embryo

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