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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.

本研究的目的是对维持生命所必需的消化器官的形态发生和上皮细胞分化进行分子生物学、细胞生物学和实验胚胎学研究。本研究对参与消化道区域化的基因、参与胃形态发生的基因、生长因子、转录因子以及与上皮-间质相互作用相关的基因进行了功能分析，我们克隆了几个基因，它们在前胃中表现出不同的表达模式，（腺胃）和肌胃（肌胃），并且表明它们的产物对于间充质的分化是重要的。特别是在腺胃和肌胃平滑肌的分化方面，我们克隆了与平滑肌分化相关的CFKBP/AMP基因。以SMAP基因的表达为标志，阐明了导致血管最外层平滑肌层形成的机制。在腺胃的形态发生和细胞分化过程中，上皮细胞分泌的表皮生长因子（EGF）和音刺猬因子（Sonic Hedgehog）起着重要作用。同时，鸡胚胃蛋白酶原基因在腺胃腺细胞中的特异性表达受sox和加塔转录因子的调控。最后，我们确定BMP 2是诱导腺胃腺和ECPg表达的重要间充质因子，因为BMP 2在间充质中的过表达极大地促进腺胃腺的形成，而BMP的拮抗剂Noggin的过表达则完全抑制腺胃腺的形成。