Molecular and developmental biological study on the gut morphogenesis and cytodifferentiation

肠道形态发生和细胞分化的分子和发育生物学研究

基本信息

批准号：
11480222
负责人：
YASUGI Sadao
金额：
$ 9.47万
依托单位：
Tokyo Metropolitan University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2002
项目状态：
已结题

项目摘要

The purpose of the present study was to carry out molecular biological, cell biological and experimental embryological research on the morphogenesis and epithelial cytodifferentiation of the digestive organs, necessary for the maintenance of life. In the present work, functional analyses of genes involved in the regionaolization of the digestive tract, genes involved in the morphogenesis of the stomach, growth factors, transcription factors and those related to the epithelial-mesenchymal interactions have been done.To obtained genes involved in the regionalization, we cloned several genes which showed different expression patterns between the proventriculus (glandular stomach) and gizzard (muscular stomach), and it was shown that their products are important for the differentiation of the mesenchyme. Especially, the differentiation of smooth muscle which is drastically different between the proventriculus and gizzard, we cloned CFKBP/AMP gene related to the smooth muscle differentiation. The mechanism that leads to the formation of smooth muscle layer in the outermost layer of the tract was elucidated with SMAP gene expression as a marker. As for the morphogenesis and cytodifferentiation of the proventriculus, it was revealed that EGF, one of the famous growth factors, and sonic hedgehog produced by epithelial cells play important roles. Also, the specific expression of the embryonic chicken pepsinogen gene in the proventricular gland cells was shown to be regulated by sox and GATA transcription factors. Lastly, we identified BMP2 as an important mesenchymal factor in inducing the proventricular glands and ECPg expression, since its over-expression in the mesenchyme greatly enhances gland formation while over-expression of Noggin, an antagonist of BMP, completely inhibits it. In summary, we could identify many key genes working during the establishment of primitive gut through the formation of functional digestive organs.

本研究的目的是对消化器官的形态发生和上皮细胞分化进行分子生物学，细胞生物学和实验性研究，这是维持生命所必需的。 In the present work, functional analyses of genes involved in the regionaolization of the digestive tract, genes involved in the morphogenesis of the stomach, growth factors, transcription factors and those related to the epithelial-mesenchymal interactions have been done.To obtained genes involved in the regionalization, we cloned several genes which showed different expression patterns between the proventriculus (glandular stomach) and gizzard (muscular stomach), and it结果表明，它们的产品对于分化间质很重要。尤其是，平滑肌的差异化在Propentriculus和Gizzard之间截然不同，我们克隆了与平滑肌分化有关的CFKBP/AMP基因。用SMAP基因表达作为标记，阐明了导致在道的最外层形成平滑肌层的机制。至于预处理的形态发生和细胞分化，据表明，上皮细胞产生的著名生长因子之一EGF和声音刺猬发挥了重要作用。同样，胚胎鸡肉蛋白原基因在前脑腺细胞中的特异性表达被证明受SOX和GATA转录因子的调节。最后，我们将BMP2确定为诱导前脑腺体和ECPG表达的重要间充质因子，因为它在间充质中的过表达极大地增强了腺体的形成，而BMP的拮抗剂Noggin的过表达则完全抑制了它。总而言之，我们可以通过形成功能消化器官在建立原始肠道期间确定许多关键基因。