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

Abstract

Oct4 and Sox2 regulate the expression of target genes such as <i>Nanog, Fgf4</i>, and <i>Utf1</i>, by binding to their respective regulatory motifs. Their functional cooperation is reflected in their ability to heterodimerize on adjacent <i>cis</i> 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 <i>Fgf4</i> Sox/Oct motif. Taking into account <i>Sox2</i> expression levels fluctuate more than <i>Oct4</i>, 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.