Pfister Sabine, Jones Vanessa J, Power Melinda, Truisi Germaine L, Khoo Poh-Lynn, Steiner Kirsten A, Kanai-Azuma Masami, Kanai Yoshiakira, Tam Patrick P L, Loebel David A F
Embryology Unit, Children's Medical Research Institute, New South Wales, Australia.
Int J Dev Biol. 2011;55(1):45-58. doi: 10.1387/ijdb.103158sp.
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.
Sox17是一种转录因子，对于维持小鼠胚胎中的定形内胚层是必需的。通过对野生型和突变型胚胎以及过表达Sox17的肝癌细胞进行表达谱分析，我们鉴定出了具有Sox17依赖性表达的基因。在Sox17基因敲除胚胎中上调且在表达Sox17的HepG2细胞中下调的基因中，有一组在发育中的肝脏中表达的基因，这表明Sox17的一个功能是抑制肝脏基因表达，这与Sox17在将定形内胚层维持在祖细胞状态中的作用相一致。与这些发现一致，当将Sox17(-/-)细胞移植到野生型宿主中时，它们对定形内胚层的贡献能力减弱。基因本体分析进一步表明，许多与心脏发育相关的基因在Sox17基因敲除胚胎中下调。这与突变胚胎中心脏的发育缺陷有关，伴随着表达Myocd的心脏祖细胞的局部缺失和前肠门的畸形。
