Multipotent cell lineages in early mouse development depend on SOX2 function.

By A. Avilion, S. Nicolis, L. Pevny, Lidia Pérez, N. Vivian, R. Lovell-Badge. Genes & Development, 2003

2,498 citations recorded by the source corpus.

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.

Subfields: Molecular Biology, Public Health, Environmental and Occupational Health

View Paper: https://www.semanticscholar.org/paper/9d061a7b8a86581724ec744df30fbc4fc6cfb721

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Citations in the corpus

Sox2+ adult stem/progenitor cells are important for tissue regeneration and survival of mice (2011, neutral): “Consistent with other reports (Avilion et al., 2003; Ellis et al., 2004), we detected strong GFP expression in blastocysts, neural progenitor cells (NPCs), and ESC cultures (Figure 1B), indicating that the knockin allele faithfully reports Sox2 expression in previously documented Sox2 cell types.”
Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. (2003, background): “The effect of Nanog is highly specific and is not reproduced by a panel of candidate cDNAs introduced into ES cells, including Oct4 and two transcription factors, Sox2 and FoxD3, identified as Oct4 partners and implicated in the pluripotency of epiblast by in vivo deletion (Hanna et al. 2002 and Av”
Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. (2006, background): “Several transcription factors, including Oct3/4 (Nichols et al., 1998; Niwa et al., 2000), Sox2 (Avilion et al., 2003), and Nanog (Chambers et al., 2003; Mitsui et al., 2003), function in the maintenance of pluripotency in both early embryos and ES cells.”
An extended transcriptional network for pluripotency of embryonic stem cells. (2008, background): “Sox2 is a transcriptional partner of Oct4 (Avilion et al., 2003).”
Lineage-specific polycomb targets and de novo DNA methylation define restriction and potential of neuronal progenitors. (2008, neutral): “, 2006a), Sox2 (Avilion et al., 2003), Nanog (Chambers et al.”
Activin/Nodal and FGF pathways cooperate to maintain pluripotency of human embryonic stem cells (2005, background): “Reversetranscriptase PCR analyses showed that the disappearance of pluripotency markers (Oct-4, FGF4 and Nodal) (Avilion et al., 2003; Vallier et al., 2004a) was blocked in the presence of these growth factors, and that the appearance of the neuroectodermal marker Neurod1 was delayed.”
Resolution of cell fate decisions revealed by single-cell gene expression analysis from zygote to blastocyst. (2010, background): “All three molecules are essential to fate decisions within the ICM (Arman et al., 1998; Avilion et al., 2003; Feldman et al., 1995), and Fgf signaling is essential to the establishment of the PE (Chazaud et al., 2006; Nichols et al., 2009).”
Pluripotency governed by Sox2 via regulation of Oct3/4 expression in mouse embryonic stem cells (2007, background): “Null mutations of each of these genes results in early embryonic lethality due to the inability to maintain pluripotent cell”
Sox2 deficiency causes neurodegeneration and impaired neurogenesis in the adult mouse brain (2004, methodology): “generated different mouse mutant alleles: a null allele ( Sox2βgeo‘knock-in’) (Zappone et al., 2000; Avilion et al., 2003), and”
Trophoblast differentiation during embryo implantation and formation of the maternal-fetal interface. (2004, background): “Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4.”
Control of Embryonic Stem Cell State (2011, background): “Oct4 functions as a heterodimer with Sox2 in ESCs, thus placing Sox2 among the key regulators (Ambrosetti et al., 2000; Avilion et al., 2003; Masui et al., 2007).”
Embryonic stem cells: prospects for developmental biology and cell therapy. (2005, background): “These included the presence of transcripts to Oct-3/4, Nanog, Tdgf1, Utf1, and lin-28 in undifferentiated hES cells, but remarkably, Sox2, Dnmt3B, gp130 and Rex-1 (ZFP42) were inconsistently or poorly expressed among several lines (31, 103, 138).”
MicroRNA-145 regulates OCT4, SOX2, and KLF4 and represses pluripotency in human embryonic stem cells. (2009, neutral): “Loss of miR-145 impairs differentiation and elevates OCT4, SOX2, and KLF4.”