The primitive endoderm lineage of the mouse blastocyst: sequential transcription factor activation and regulation of differentiation by Sox17.
The primitive endoderm lineage of the mouse blastocyst: sequential transcription factor activation and regulation of differentiation by Sox17.
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DOI：
10.1016/j.ydbio.2010.12.007
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发表时间：
2011-02-15
影响因子：
2.7
通讯作者：
Hadjantonakis AK
中科院分区：
文献类型：
--
作者：
Artus J;Piliszek A;Hadjantonakis AK
原始内胚层细胞（PrE）和多能外胚层细胞（EPI）是小鼠囊胚期胚胎内细胞团（ICM）中指定的两个细胞系，在着床前阶段结束时分化成相邻的组织层。前胚层是靠近囊胚腔的极化上皮，基底膜将其与外胚层分开，有两个衍生物，内脏和顶叶内胚层。在这项研究中，我们研究了SOX家族的两个转录调控因子SOX17和SOX7在PrE及其衍生物中的定位。我们注意到SOX17首先在ICM内的盐和胡椒分布中被检测到，随后局限于新生的PrE上皮。SOX17的这种动态分布类似于另外两个PrE谱系特异性转录因子GATA6和GATA4的定位。相比之下，SOX7仅在与囊胚接触的PrE细胞中检测到，这增加了这些细胞在分子上不同的可能性。我们的观察结果支持PrE谱系中顺序GATA6 > SOX17 > GATA4 > SOX7转录因子激活的模型，这可能与细胞谱系“naïvete”、承诺和分选的连续周期有关。此外，我们的数据表明，在分选的PrE细胞中，SOX17和SOX7的共表达可以解释SOX17突变囊胚缺乏可检测的表型。然而，对着床延迟囊胚的分析显示，SOX17在维持PrE上皮完整性方面发挥作用，缺乏SOX17会导致顶叶内胚层过早剥离和迁移。
Cells of the primitive endoderm (PrE) and the pluripotent epiblast (EPI), the two lineages specified within the inner cell mass (ICM) of the mouse blastocyst stage embryo, are segregated into adjacent tissue layers by the end of the preimplantation period. The PrE layer which emerges as a polarized epithelium adjacent to the blastocoel, with a basement membrane separating it from the EPI, has two derivatives, the visceral and parietal endoderm. In this study we have investigated the localization of two transcriptional regulators of the SOX family, SOX17 and SOX7, within the PrE and its derivatives. We noted that SOX17 was first detected in a salt-and-pepper distribution within the ICM, subsequently becoming restricted to the nascent PrE epithelium. This dynamic distribution of SOX17 resembled the localization of GATA6 and GATA4, two other PrE lineage-specific transcription factors. By contrast, SOX7 was only detected in PrE cells positioned in contact with the blastocoel, raising the possibility that these cells are molecularly distinct. Our observations support a model of sequential GATA6 > SOX17 > GATA4 > SOX7 transcription factor activation within the PrE lineage, perhaps correlating with the consecutive periods of cell lineage ‘naïvete’, commitment and sorting. Furthermore our data suggest that co-expression of SOX17 and SOX7 within sorted PrE cells could account for the absence of a detectable phenotype of Sox17 mutant blastocysts. However, analysis of implantation-delayed blastocysts, revealed a role for SOX17 in the maintenance of PrE epithelial integrity, with the absence of SOX17 leading to premature delamination and migration of parietal endoderm.
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作者：
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