Multipotent cell lineages in early mouse development depend on SOX2 function
Multipotent cell lineages in early mouse development depend on SOX2 function
复制标题
DOI：
10.1101/gad.224503
复制
发表时间：
2003-01-01
影响因子：
10.5
通讯作者：
Lovell-Badge, R
中科院分区：
文献类型：
--
作者：
Avilion, AA;Nicolis, SK;Lovell-Badge, R
哺乳动物植入前胚胎中特化的每个细胞谱系的发育都依赖于内在因素，但它们之间也相互依存。OCT4是内细胞团/上胚层谱系所必需的，对胚外内胚层在短暂的高水平时是必需的，而且通过其在调节Fgf4表达中的作用，对从极性滋养外胚层建立和增殖胚外外胚层也是间接必需的。转录因子SOX2也参与了Fgf4表达的调节。我们利用基因打靶技术使Sox2失活，检查了突变胚胎以及用上胚层被野生型胚胎干细胞拯救的嵌合体中的表型结果。我们发现该基因在上胚层和胚外外胚层中分别对所有胚胎细胞类型和滋养层细胞类型的多能前体细胞有细胞自主性需求。然而，在ICM内的早期作用可能因母源蛋白的持续存在而被掩盖，而SOX2的缺乏在交配后7.5天之后才在绒毛膜中变得至关重要。我们的数据表明，母源成分可能参与建立早期细胞命运决定，并且一个需要SOX2和OCT4的组合密码决定了着床时存在的最初三个谱系。
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 lCM 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.