Sox17-dependent gene expression and early heart and gut development in Sox17-deficient mouse embryos
Sox17-dependent gene expression and early heart and gut development in Sox17-deficient mouse embryos
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DOI：
10.1387/ijdb.103158sp
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发表时间：
2011-01-01
影响因子：
0.7
通讯作者：
Loebel, David A. F.
中科院分区：
文献类型：
--
作者：
Pfister, Sabine;Jones, Vanessa J.;Loebel, David A. F.
Sox 17是维持小鼠胚胎定形内胚层所需的转录因子。通过野生型和突变型胚胎和Sox 17过表达肝癌细胞的表达谱分析，我们确定了Sox 17依赖性表达的基因。在Sox 17缺失胚胎中上调和表达Sox 17的HepG 2细胞下调的基因中，有一组基因在发育中的肝脏中表达，这表明Sox 17的一个功能是抑制肝脏基因表达，这与Sox 17在维持定形内胚层处于祖细胞状态中的作用是一致的。与这些发现一致，Sox 17（-/-）细胞在移植到野生型宿主中时显示出对定形内胚层的贡献能力减弱。基因本体分析进一步揭示了许多与心脏发育相关的基因在Sox 17缺失的胚胎中表达下调。这与突变胚胎中心脏的发育缺陷有关，伴随着表达Myocd的心源性祖细胞的局部丧失和前肠门的畸形。
Sox17 is a transcription factor that is required for maintenance of the definitive endoderm in mouse embryos. By expression profiling of wild-type and mutant embryos and Sox17-overexpressing hepatoma cells, we identified genes with Sox17-dependent expression. Among the genes that were up-regulated in Sox17-null embryos and down-regulated by Sox17-expressing HepG2 cells is a set of genes that are expressed in the developing liver, suggesting that one function of Sox17 is the repression of liver gene expression, which is compatible with a role for Sox17 in maintaining the definitive endoderm in a progenitor state. Consistent with these findings, Sox17(-/-) cells display a diminished capacity to contribute to the definitive endoderm when transplanted into wild-type hosts. Analysis of gene ontology further revealed that many genes related to heart development were downregulated in Sox17-null embryos. This is associated with the defective development of the heart in the mutant embryos, which is accompanied by localised loss of Myocd-expressing cardiogenic progenitors and the malformation of the anterior intestinal portal.