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

假定的外胚层产生表皮或自然组织，并且命运决定是在原肠胚形成期间做出的。自从1920年代Spemann和Mangold的实验表明，两栖动物的背唇在植入腹侧时可以诱导包括大脑和眼睛在内的神经组织的次级身体轴。在宿主胚胎的一侧，神经组织被认为是在胚胎背唇区域发出的因素触发的诱导下形成的，然而，最近对其功能的研究。多肽生长因子的研究表明，不是外胚层而是神经形成是基态。也就是说，外胚层注定要形成神经组织，除非它被BMP诱导成为表皮。此外，最近表明神经诱导的发生是因为。 BMP 活性受到其结合蛋白（如头蛋白和脊索蛋白）的抑制。在这项研究中，我们表明，最初被称为激活素结合蛋白的卵泡抑素能够结合 BMP……更多卵泡抑素抑制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之间的相互作用，并发现复合物的解离非常快，这使得检测卵泡抑素与BMP之间的相互作用并发现卵泡抑素的解离。该复合物速度非常快，这使得通过常规生化方法检测相互作用变得困难。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导的。为了阐明BMP的细胞内信号传导机制，我们筛选了BMP的信号分子和靶基因。我们首先鉴定了一种新的MAPKKK TAK1作为非洲爪蟾BMP信号的介质。因为显性失活（激酶阴性）TAK1的过度表达。神经诱导的命运，TAK1 被认为是 BMP 信号的介导者，我们鉴定了 homebox 基因 msx-1 作为对 BMP-2 做出反应的早期基因。 BMP-4。我们进一步证实msx-1的过度表达导致了BMP功能获得的表型。我们的研究阐明了BMP信号在神经抑制途径中的一部分。