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MOLECULAR MECHANISM FOR NEURAL FROMATION BY BMP

BMP 神经形成的分子机制

基本信息

批准号：
08458236
负责人：
UENO Naoto
金额：
$ 4.67万
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 Scientific Research (B)
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

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08458236/
关键词：
BONE MORPHOGENETIC PROTEIN NEURAL INDUCTION XENOPUS LAEVIS TGF-B SUPERFAMILY TAK1 MSX-1 EPIDERMIS INTRACELLULAR SIGNALING オ-ガナイザー Ser Thrキナーゼ受容体フオリスタチン

项目摘要

Presumptive ectoderm gives rise to epidermal or naural tissues and the fate determination is made during gastrulation. Since after the experiments by Spemann and Mangold in 1920's showing that dorsal lip of amphibian can induce secondary body axis with neural tissues including brain and eyes when implanted in ventral side of host embryo, neural tissues are believed to be formed upon the induction triggered by factors emanated from the dorsal lip region of the embryo. However, recent studies on the function of polupeptide growth factors revealed that not epiudemal but neural formation is the ground state. Namely, ectodem is fated to become neural tissue is formed unless it is induced to become epidemis by BMP.Furthemore, it has recently been shown that neural induction takes place because BMP activity is inhibited by its binding proteins such as noggin and chordin.In this study, we have shown that follistatin which was originally known as an activin-binding protein, is able to bind BMP … More Thus follistatin inhibits epidermal inducging activity of BMP thereby induces neural fate. We further confirmed that tyhe interaction between follistatin and BMP and found that the dissociation of the complex is very fast, which makes detection of the interaction between follistatin and BMP and found that the dissociation of the complex is very fast, which makes detection of the interaction by conventional biochemical way difficult. The signal of BMP is mediated through cell surface ser/thr kinase recepotrs and intracellular mediators. To clarify the intyracellular signaling mechanism of BMP,we have screened for signaling moleculeS and target gene of BMP.We first identified a novel MAPKKK TAK1 as a mediater of BMP signal in Xenopus.Because overexpression of a dominant negative (kinase negatuive) TAK1 induced neural fate, TAK1 was suggested to be a mediatoR of BMP signal. We identified a homebox gene msx-1 as an immediate early gene responding to BMP-2 and BMP-4. We further confirmed that msx-1 overexpression leads to the phenotype reminicent to gain-of function of BMP.Our study has clarified a part of BMP signaling in the pathway of neural inhibition. Less

推测外胚层形成表皮或神经组织，并在原肠形成过程中决定命运。自从1920年S的实验表明，两栖动物的背唇植入宿主胚胎腹侧时，可以与包括脑和眼睛在内的神经组织一起诱导次级体轴，因此人们认为神经组织的形成是由胚胎背唇区的因素触发的。然而，最近对多肽生长因子功能的研究表明，神经形成是基态，而不是外膜。在这项研究中，我们已经证明，最初被称为激活素结合蛋白的卵泡抑素能够与骨形态发生蛋白…结合此外，卵泡抑素抑制BMP的表皮诱导活性，从而诱导神经命运。我们进一步证实了卵泡抑素与BMP的相互作用，发现该复合体的解离速度很快，这使得检测卵泡抑素与BMP的相互作用变得非常迅速，这使得用常规的生化方法检测这种相互作用变得困难。BMP信号是通过细胞表面丝氨酸/苏氨酸激酶受体和细胞内介质介导的。为了阐明BMP的细胞内信号机制，我们筛选了BMP的信号分子和靶基因。我们首次在非洲爪哇中发现了一个新的MAPKKK TAK1作为BMP信号的中介体。由于一个显性的负性(激酶负性)TAK1的过表达诱导了神经命运，因此TAK1被认为是BMP信号的中介体。我们发现同源盒基因MSX-1是对BMP-2和BMP-4有反应的即刻早期基因。我们进一步证实了MSX-1的过表达导致了BMP功能增强的表型。我们的研究阐明了BMP信号通路中的一部分。较少