Dynamic changes in Sox2 spatio-temporal expression promote the second cell fate decision through Fgf4/Fgfr2 signaling in preimplantation mouse embryos

Tapan Kumar Mistri, Wibowo Arindrarto, Wei Ping Ng, Choayang Wang, Leng Hiong Lim, Lili Sun, Ian Chambers, Thorsten Wohland, Paul Robson

Research output: Contribution to journalArticlepeer-review

Abstract

Oct4 and Sox2 regulate the expression of target genes such asNanog, Fgf4, and Utf1, by binding to their respective regulatory motifs. Their functional cooperation is reflected in their ability to heterodimerize on adjacent cis regulatory motifs, the composite Sox/Oct motif. Given that Oct4 and Sox2 regulate many developmental genes, a quantitative analysis of their synergistic action on different Sox/Oct motifs would yield valuable insights into the mechanisms of early embryonic development. In the present study, we measured binding affinities of Oct4 and Sox2 to different Sox/Oct motifs using fluorescence correlation spectroscopy. We found that the synergistic binding interaction is driven mainly by the level of Sox2 in the case of the Fgf4 Sox/Oct motif. Taking into account Sox2 expression levels fluctuate more than Oct4, our finding provides an explanation on how Sox2 controls the segregation of the epiblast and primitive endoderm populations within the inner cell mass of the developing rodent blastocyst.

Original languageEnglish
Pages (from-to)1075-1089
Number of pages15
JournalBiochemical Journal
Volume475
Issue number6
DOIs
Publication statusPublished - 20 Mar 2018

Keywords

  • Oct4
  • Sox/Oct motif
  • cooperativity
  • fluorescence correlation spectroscopy (FCS)

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