The role of Sox 17 during mouse gut formation.

Sox （SRY相关HMG盒子）基因家族是通过其与性别决定因素基因SRY的高迁移群（HMG）盒子的同源性首次被发现的。Sox家族的成员已经在各种脊椎动物中分离出来，包括人类和小鼠中的20个Sox基因。该基因家族的成员编码转录因子，在各种发育过程中调节细胞类型和组织分化的规范。对Sox17表达的分析显示，它在植入后小鼠胚胎的内脏和最终内胚层中具有活性。在本项目中，我们研究了Sox17在小鼠内胚层源性肠道形成中的作用。Sox17 mRNA首先在确定的全肠内胚层表达，可能在未来的前肠中作为维持因子，在中肠和后肠中作为分化调节因子。晚期，Sox17 mRNA在肝憩室表达。杂合子胚胎的肝脏也表现出叶周围区域的改变。观察到的主要表型是肝脏近似重量的减少。这是一个初步的数据，但遗传背景对肝功能不全的影响需要在进一步的研究中观察。我们的观察结果强烈表明，Sox17在哺乳动物细胞进入内胚层及其衍生器官的决定中起着关键作用。这些发现提示，Sox17可能是未来人类治疗性研究中分离内胚层干细胞和获得胚胎干细胞衍生内胚层细胞的关键基因之一。

The Sox (Sry-related HMG box) gene family was first identified through its homology to the high mobility group (HMG) box of the sex determining factor gene SRY. Members of the Sox family have been isolated in various vertebrate species, including 20 Sox genes in humans and mice. Members of this gene family encode transcription factors that regulate the specification of cell types and tissue differentiation in various developmental processes. Analyses of Sox17 expression have revealed activity in the visceral and definitive endoderm of post-implantation mouse embryos. In this project, we have studied that the role of Sox17 on the mouse endoderm derived gut formation. mRNA of Sox17 is expressed on definitive entire gut endoderm at first, and may function as a maintenance factor in prospective foregut, and differenaitation regulator at mid and hindgut. The later stage, mRNA of Sox17 is expressed on hepatic diverticum. The liver from the heterozygous embryo also shows the alteration of peripheral region of lobes. The major phenotype observed is the decrease of approximate weight of the liver. This is a preliminary data, but the effect of genetical backrgound to the hepato-insufficisncycy are necessary to be observed in the further study. Our observation strongly indicate that a critical role of Sox17 in the determination of the cell into the endoderm and its derivative organ in mammals. These findings lead us to the possibility that Sox17 is one of the key genes for the isolation of the endodermal stem cells and obtaining of the endodermal cells derived from ES cells in the human therapeutic research for the future.