MOLECULAR MECHANISM OF EARLY DEVELOPMENTAL PATTERNING BY TGF-B FACTORS

TGF-B 因子影响早期发育模式的分子机制

基本信息

批准号：
08044185
负责人：
UENO Naoto
金额：
$ 3.58万
依托单位：
NATIONAL INSTITUTE FOR BASIC BIOLOGY (NIBB) (1997)Hokkaido University (1996)
依托单位国家：
日本
项目类别：
Grant-in-Aid for international Scientific Research
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

项目摘要

In the late 80's, it has been proposed that polypeptide growth factors are playing essential roles in the regulation of early development. Since then extensive studies on the function of growth factors in the paterning of embryo have been carried out by developmental biologists. Studies using Xenopus laevis clarified that growth factors are involved in at least two inductions, cell-to-cell interactions controlling early embryogenesis. They are mesoderm induction and neural induction. During the course of this collaboration program, we have shown that members of TGF-b superfamily activin and Vgl can induce dorsal mesoderm such as notochord and muscle. In contrast another member of the TGF-b family, bone morphogenetic protein (BMP) was shown to induce ventral mesoderm such as blood.The other induction, neural induction was found to be regulated by BMP.BMP appears to inhibit neural induction of ectoderm by inducing epidermis. We proposed a model that Xenopus ectoderm is fated to become naural tunless the neural fate is inhibited by ventrally located BMP activity. This model further suggests that neural fate is a default state. Recent study identified BMP-binding proteins such as noggin, chordin, and follistatin to be BMP-binding poteins, which is therefore acting as neural inducers.Finally, we have also identified componets acting in the pathway regulated BMP.They include receptors for acrtivin and BMP,both of which are Ser/Thr kinases, Smad, and a novel MAPKKK,TAKI.We have shown that they also play important roles in early embryogenesis acting down stream of BMP.Particularly, homeobox gene Msx-1 was shown to mimick the action of BMP : over expression of Msx-1 in dorsal blastomeres of Xenopus ventralizes the embryo.Together, we believe our effort in this international collaboration clarified important part of moleauclr mechanism of growth factor function in the regulation of early development.

八十年代末，有人提出多肽生长因子在早期发育的调节中发挥重要作用。从那时起，发育生物学家对生长因子在胚胎模式中的功能进行了广泛的研究。使用非洲爪蟾的研究阐明，生长因子参与至少两种诱导，即控制早期胚胎发生的细胞间相互作用。它们是中胚层诱导和神经诱导。在这个合作项目的过程中，我们已经证明TGF-b超家族激活素和Vgl的成员可以诱导背侧中胚层，例如脊索和肌肉。相比之下，TGF-b家族的另一个成员，骨形态发生蛋白（BMP）被证明可以诱导腹侧中胚层，例如血液。另一种诱导，神经诱导被发现受BMP调节。BMP似乎通过以下方式抑制外胚层的神经诱导：诱导表皮。我们提出了一个模型，即非洲爪蟾外胚层注定要变成神经性的，除非神经命运受到位于腹侧的 BMP 活性的抑制。该模型进一步表明神经命运是默认状态。最近的研究确定了 BMP 结合蛋白，如 noggin、chordin 和 follistatin 是 BMP 结合蛋白，因此可作为神经诱导剂。最后，我们还确定了在 BMP 调节途径中起作用的成分。它们包括活性素和卵泡抑素的受体。 BMP，两者都是 Ser/Thr 激酶 Smad 和一种新型 MAPKKK，TAKI。我们已经证明它们在早期胚胎发生中也发挥着重要作用，作用于下游BMP。特别是，同源框基因 Msx-1 被证明可以模仿 BMP 的作用：Msx-1 在非洲爪蟾背卵裂球中的过度表达使胚胎腹侧化。我们相信，我们在这项国际合作中的努力阐明了 Moeauclr 机制的重要部分。生长因子在调节早期发育中发挥作用。