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

假性外胚层会产生表皮或新组织，并且在胃静脉期间确定脂肪。自从Spemann和Mangold在1920年的实验之后，表明两栖动物的背唇可诱导继发体轴，当植入宿主胚胎的腹侧时，包括脑和眼睛，包括脑和眼睛，神经组织的神经组织，被认为是由从Dorsal Lip区域触发的因素触发的。然而，关于核苷酸生长因子功能的最新研究表明，不是上型，而是神经形成是基态。 Namely, ectodem is fated to become neuronal tissue is formed unless it is induced to become epidemis by BMP.Furthemore, it has recently been shown that neuroinduction 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 …follistatin抑制BMP的表皮活性的更多信息会诱导神经命运。我们进一步证实，follistatin和BMP之间的相互作用，发现该复合物的解离非常快，这使得通过常规生化方法难以检测到这种相互作用。 BMP的信号通过细胞表面SER/THR激酶回收和细胞内介体介导。为了阐明BMP的肠细胞信号传导机制，我们筛选了BMP的信号分子和靶基因。我们首先将新型的MAPKKKKKK tak1确定为Xenopus中BMP信号的媒介。视外表达过度表达，因为the1诱导的神经效果的主要负面（激酶负）诱导的信号，tak1 tak1 tak1 tak1 tak1 the bmp bmp bmp bmp bmp bmp bmp bmp bmp。我们将Homebox基因MSX-1确定为对BMP-2和BMP-4响应的直接早期基因。我们进一步证实，MSX-1的过表达导致了BMP的功能的表型。较少的