Multipotent cell lineages in early mouse development depend on SOX2 function

TLDR

Cell lineage specification in the preimplantation mouse embryo depends on intrinsic factors and mutual interdependence, with OCT4 required for ICM/epiblast and extraembryonic endoderm and regulating Fgf4 for extraembryonic ectoderm, while SOX2 has also been implicated in Fgf4 regulation. The authors used Sox2 gene targeting to generate mutant embryos and chimeras with wild‑type epiblast rescue to assess phenotypic consequences. SOX2 is cell‑autonomously required for epiblast and extraembryonic ectoderm development, with maternal SOX2 masking an earlier ICM role; its absence becomes critical in the chorion after 7.5 dpc, suggesting maternal components help establish early fate decisions and that a SOX2–OCT4 combinatorial code specifies the first three implantation lineages.

Abstract

Each cell lineage specified in the preimplantation mammalian embryo depends on intrinsic factors for its development, but there is also mutual interdependence between them. OCT4 is required for the ICM/epiblast lineage, and at transient high levels for extraembryonic endoderm, but also indirectly through its role in regulating Fgf4 expression, for the establishment and proliferation of extraembryonic ectoderm from polar trophectoderm. The transcription factor SOX2 has also been implicated in the regulation of Fgf4 expression. We have used gene targeting to inactivate Sox2 , examining the phenotypic consequences in mutant embryos and in chimeras in which the epiblast is rescued with wild-type ES cells. We find a cell-autonomous requirement for the gene in both epiblast and extraembryonic ectoderm, the multipotent precursors of all embryonic and trophoblast cell types, respectively. However, an earlier role within the ICM may be masked by the persistence of maternal protein, whereas the lack of SOX2 only becomes critical in the chorion after 7.5 days postcoitum. Our data suggest that maternal components could be involved in establishing early cell fate decisions and that a combinatorial code, requiring SOX2 and OCT4, specifies the first three lineages present at implantation.