A cell-autonomous activity of mouse Sox17 gene in mouse embryogenesis

小鼠 Sox17 基因在小鼠胚胎发生中的细胞自主活性

基本信息

批准号：
13660295
负责人：
KANAI Yoshiakira
金额：
$ 2.18万
依托单位：
THE UNIVERSITY OF TOKYO
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13660295/
关键词：
Sox17 Endoderm ES cells Gut ノックアウトマウス

项目摘要

In the mouse, the definitive endoderm is derived the epiblast during gastrulation, and, at the early organogenesis stage, forms the primitive gut tube, which gives rise to the digestive tract, liver, pancreas and associated visceral organs. The transcriptional factors, Sox17 (a Sry-related HMG box factor) and its upstream factors, Mixer and Casanova, have been shown to function as endoderm determinants in Xenopus and zebrafish, respectively. However, whether the mammlian orthologues of these genes are also involved with endoderm formation is not known. We show that Sox17^<-/-> mutant embryos are deficient of gut endoderm. The earliest recognisable defect is the reduced occupancy by the definitive endoderm in the posterior and lateral region of the prospective mid-and hundgut of the headfold stage embryo. The prospective forgut develops properly until the late neural place stage. Thereafter, elevated levels of apoptosis lead to a reductin in the population of the definitive endoderm in the forgut. In addition, the mid- and hingut tissues fail to expand. These are accompanied by the replacement of the definitive endoderm in the lateral region of the entire length of the embryonic gut by cells that resemble the visceral endoderm. In the chimeras, although Sox17-null ES cells can contribute unrestrictedly to ectoderm and mesodermal tissues, few of them could colonize the forgut endoderm and they are completely excluded from the mid- and hindgut endoderm. Our findings indicate an important role of Sox17 in endoderm development in the mouse, highlighting the idea that the molecular mechanisms for endoderm formation in likely to be conserved among vertebrates.

在小鼠中，定形内胚层在原肠胚形成过程中衍生为外胚层，并在早期器官发生阶段形成原始肠管，产生消化道、肝脏、胰腺和相关内脏器官。转录因子 Sox17（一种与 Sry 相关的 HMG 盒因子）及其上游因子 Mixer 和 Casanova 已被证明分别在非洲爪蟾和斑马鱼中发挥内胚层决定簇的作用。然而，这些基因的哺乳动物直系同源物是否也参与内胚层形成尚不清楚。我们发现 Sox17^</-/-> 突变体胚胎缺乏肠道内胚层。最早可识别的缺陷是头折阶段胚胎的预期中肠和肠肠的后部和外侧区域中定形内胚层的占有率减少。预期前肠正常发育直至晚期神经位置阶段。此后，细胞凋亡水平升高导致前肠定形内胚层群体减少。此外，中段和后段组织无法扩张。这些伴随着胚胎肠道整个长度的侧面区域中的定形内胚层被类似于内脏内胚层的细胞取代。在嵌合体中，尽管Sox17缺失的ES细胞可以不受限制地形成外胚层和中胚层组织，但它们中很少有可以定植于前肠内胚层，并且它们完全被排除在中肠和后肠内胚层之外。我们的研究结果表明 Sox17 在小鼠内胚层发育中的重要作用，强调了内胚层形成的分子机制可能在脊椎动物中保守的观点。