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.

增长因素与早期发展的调节有关。尽管激活素是TGF-beta相关生长因子家族的成员作为垂体细胞的FSH分泌的刺激剂，但最近已显示出来从Xenopus laevis的推定外胚层诱导中胚层组织。为了更准确地理解中胚层诱导的分子机制，我们已经筛选了Xenopus laevis的基因组DNA文库，并用大鼠激活素βAlpha基因作为探针。我们已经分离出5个独立的基因，其中一个基因正在编码与哺乳动物激活素密切相关的蛋白质。有趣的是，其余基因包含两栖动物的哺乳动物骨形态发生蛋白的两栖动物，该蛋白是根据它们在体内诱导异位骨形成的能力而纯化的。最终，我们通过将其RNA的RNA注射到早期的胚泡早期Xenopus胚胎中，以查看其基因产物的过度表达的效果，从而对生长因子CDNA进行了锻炼分析，从而分离了异爪蟾激活素的cDNA。腹侧一半中激活素的过表达导致人体轴重复，表明激活素在背面中起作用。另一方面，背面半中BMP-4的表达抑制了前后结构的形成，这表明BMP对腹膜可能很重要。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。