title: Multipotent cell lineages in early mouse development depend on SOX2 function.
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.
authors.affiliation: Division of Developmental Genetics, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
authors.forename: Ariel A
authors.initials: AA
authors.lastname: Avilion
authors.forename: Silvia K
authors.initials: SK
authors.lastname: Nicolis
authors.forename: Larysa H
authors.initials: LH
authors.lastname: Pevny
authors.forename: Lidia
authors.initials: L
authors.lastname: Perez
authors.forename: Nigel
authors.initials: N
authors.lastname: Vivian
authors.forename: Robin
authors.initials: R
authors.lastname: Lovell-Badge
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000378:metabolism; D019070:Cell Lineage / Q000235:genetics*; D002678:Chimera; D002823:Chorion / Q000166:cytology; D003433:Crosses, Genetic; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D004475:Ectoderm / Q000166:cytology; D004624:Embryo Transfer; D005314:Embryonic and Fetal Development / Q000235:genetics; D005260:Female; D005346:Fibroblast Growth Factors / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D005804:Genes, Lethal; D024002:HMGB Proteins; D006579:Heterozygote; D008297:Male; D008431:Maternal-Fetal Exchange; D051379:Mice; D018613:Microscopy, Confocal; D039902:Multipotent Stem Cells / Q000166:cytology*; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D050814:Octamer Transcription Factor-3; D010641:Phenotype; D011247:Pregnancy; D055748:SOXB1 Transcription Factors; D014157:Transcription Factors; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D024002:HMGB Proteins; D009687:Nuclear Proteins; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D014157:Transcription Factors; C112971:fibroblast growth factor 14; D005346:Fibroblast Growth Factors