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Studies on the role of growth factors in embryonic inductions

生长因子在胚胎诱导中作用的研究

基本信息

批准号：
03833001
负责人：
UENO Naoto
金额：
$ 1.15万
依托单位：
University of Tsukuba, Institute of Applied Biochemistry
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1992
项目状态：
已结题

项目摘要

Growth factors have been implicated in the regulation of early development. Although activin,a member of TGF-beta related growth factor family was discovered as a stimulator of FSH secretion from pituitary cells,it has recently been shown to induce mesodermal tissues from presumptive ectoderm of Xenopus laevis. In order to understand more precisely the molecular mechanism of the mesoderm induction,we have screened a genomic DNA library of Xenopus laevis with rat activin betaALPHA gene as a probe. We have isolated 5 independent genes and one of the genes was found to be encoding a protein closely related to mammalian activin. Interestingly,the rest of the gene contained an amphibian counterpart of mammalian bone morphogenetic proteins, which was purifed based on their ability to induce ectopic bone formation in vivo. Eventually,we isolated cDNAs of Xenopus activin,BMP-2,-4 and -7.Functional analysis has been performed for the growth factor cDNAs by injecting their RNA into early blastomeres early Xenopus embryos to see the effect of overexpression of their gene product. Overexpression of activin in ventral half resulted in duplication of body axis,suggesting that activin play a role in dorsalization. On the other hand,over expression of BMP-4 in dorsal half inhibited the formation of anterior and dorsal structure,suggesting that BMP may be important for ventralization. These results suggest that activin and BMP have distinct role in pattern formation of early embryos.

生长因子与早期发育的调节有关。虽然激活素是TGF-β相关生长因子家族的一员，被发现是垂体细胞分泌FSH的刺激物，但最近发现它可以诱导非洲爪蟾（Xenopus laevis）的假定外胚层形成中胚层组织。为了更准确地了解中胚层诱导的分子机制，我们以大鼠激活素β-ALPHA基因为探针，对非洲爪蟾基因组DNA文库进行了筛选。我们已经分离出5个独立的基因，其中一个基因被发现编码与哺乳动物激活素密切相关的蛋白。有趣的是，该基因的其余部分含有哺乳动物骨形态发生蛋白的两栖动物对应物，该蛋白是基于它们在体内诱导异位骨形成的能力而纯化的。最后，我们分离了非洲爪蟾激活素、BMP-2、BMP-4和BMP-7的cDNA。通过将它们的RNA注射到非洲爪蟾早期胚胎的早期卵裂球中，对它们的基因产物进行了功能分析。激活素在腹侧过表达导致体轴重复，提示激活素在背侧化中起作用。另一方面，BMP-4在背侧的过度表达抑制了前、背侧结构的形成，提示BMP可能在腹侧化中起重要作用。这些结果表明，激活素和BMP在早期胚胎的模式形成中具有不同的作用。