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

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

doi:10.1042/bcj20170418

Abstract

Oct4 and Sox2 regulate the expression of target genes such as Nanog, 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.

Highlights

The mouse preimplantation embryo is a widely used mammalian model to study cell differentiation
Sox2 levels continue to recede in the TE, whereas there is an increase in Sox2 from the morula to inner cell mass (ICM) (Figure 1C)
We provide evidence in support of a model in which temporal alterations in the Sox2 concentration differentially regulate expression of Fgf4 and Fgfr2, thereby driving segregation of ICM into primitive endoderm (PE) and EPI

Summary

Introduction

The mouse preimplantation embryo is a widely used mammalian model to study cell differentiation. Two of the earliest cell fate decisions in mammalian development take place in the preimplantation embryo. The first decision occurs at the 16–32 cell stage and sets apart the morula into two distinct lineages: the trophoblast, represented by the trophectoderm (TE) and the inner cell mass (ICM). At this stage, the TE is a single layer of epithelial cells enclosing the early blastocyst. Cells of the PE lineage subsequently differentiate into the extra-embryonic cells responsible for secreting patterning cues and providing nutrition to the developing embryo proper which consists of cells entirely from the EPI lineage

Methods

Results

Conclusion