Studies on the role of growth factors in embryonic inductions

生长因子与早期发育的调控有关。激活素是tgf - β相关生长因子家族的一员，它被发现是垂体细胞促卵泡刺激素分泌的刺激物，最近它被证明可以诱导非洲爪蟾外胚层的中胚层组织。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 α基因为探针，筛选了非洲爪蟾基因组DNA文库。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一种与哺乳动物激活蛋白密切相关的蛋白质。有趣的是，该基因的其余部分包含一种两栖动物的哺乳动物骨形态发生蛋白，这种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，我们分离出爪蟾激活蛋白、BMP-2、-4和-7的cdna。通过将生长因子cdna的RNA注射到早期卵裂球早期爪蟾胚胎中，对其进行功能分析，观察其基因产物过表达的影响。激活素在腹侧的过度表达导致体轴的重复，表明激活素在背侧化中起作用。另一方面，BMP-4在背侧的过表达抑制了前侧和背侧结构的形成，这表明BMP可能对腹侧化很重要。这些结果表明，激活素和BMP在早期胚胎模式形成中具有不同的作用。

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.