Molecular cascades underlying the integration of cell differentiation and morphogenesis in cranial/cardiac neural crest development

颅/心脏神经嵴发育中细胞分化和形态发生整合的分子级联

• 批准号: 16390218
• 负责人: KURIHARA Hiroki
• 金额: $ 9.15万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390218/
• 关键词: Neural crest cells; Pharyngeal arch; Cardiovascular development; Embryo genesis; Endothelin; Homeotic genes; Calpain; Transcriptional factors; 細胞内シグナル; 心血管発生; 細胞分化; 形態形成; Dlx

1.We have found that endothelin-1, produced by pharyngeal epithelium and core mesoderm, acts on cranial neural crest cells via ET-A receptor (ETAR) and determines the ventral identity of the anterior pharyngeal arches by inducing homeotic genes Dlx5 and Dlx6. After the regional specification by ET-1, Dlx5/6 expression was proved to be maintained by the FGF signaling.2.We have found that the ET-1 signaling activates the enhancer activity of m5/6i, the intergenic element of the Dlx5/6loci, leading to the upregulation of Dlx5/6 expression.3.We have established mice expressing GFP under the ETAR gene promoter to visualize the ETAR-expressing cells. We also realized the transgenic mouse system in which any genes of interest can be efficiently knocked-in into the ETAR locus by Cre recombinase-mediated cassette exchange. Using this system, we could knock-in the lacZgene to definitely identify the ETAR-expressing cells.4.We have identified Capn6 as a gene downstream to the ET-1 signaling using DNA microarray. Capn6 was found to be possibly involved in cell division and morphology through the regulation of microtubular networks.5.We have identified TAZ, a transcriptional coactivator, as a Pax3-binding protein. TAZ was found to coactivate the transcriptional activity of Pax3. TAZ-lacZ knock-in mice have identified TAZ expressing cells during embryogenesis. Partial lethality of TAZ-lacZ knock-in mice has indicated the importance of this gene in development.

1.我们发现，咽上皮和核中胚层产生的内皮素-1通过ET-A受体（ETAR）作用于颅神经crest细胞，并通过诱导家用性基因DLX5和DLX6诱导前咽弓的腹侧腹弓的腹侧认同。在ET-1的区域规范之后，DLX5/6表达被证明是由FGF信号传导维持的。2。我们发现，ET-1信号激活M5/6i的增强子活性，M5/6i（DLX5/ 6loci，导致DLX5/6表达的上调。3。我们已经在ETAR基因启动子下建立了表达GFP的小鼠，以可视化表达ETAR的细胞。我们还意识到了转基因小鼠系统，其中任何感兴趣的基因都可以通过CRE重组酶介导的盒式磁带的交换有效地击中ETAR基因座。使用该系统，我们可以敲入LACZGENE，可以肯定地识别表达ETAR的细胞。4。我们已使用DNA微阵列将CAPN6识别为ET-1信号下游的基因。发现CAPN6可能通过调节微管网络参与细胞分裂和形态。5。我们已经确定转录共激活因子TAZ是PAX3结合蛋白。发现TAZ共同激活PAX3的转录活性。 Taz-Lacz敲入小鼠在胚胎发生过程中已经鉴定出TAZ表达细胞。 Taz-Lacz敲入小鼠的部分致死性表明该基因在发育中的重要性。

项目成果

Glycogen debranching enzyme association with beta-subunit regulates AMP-activated protein kinase activity.

• DOI: 10.1152/ajpendo.00003.2005
• 发表时间: 2005-05
• 期刊: American journal of physiology. Endocrinology and metabolism
• 作者: H. Sakoda;M. Fujishiro;Junko Fujio;N. Shojima;T. Ogihara;A. Kushiyama;Y. Fukushima;M. Anai;Hiraku Ono;M. Kikuchi;N. Horike;A. Viana;Y. Uchijima;H. Kurihara;T. Asano

Differential cooperation between dHAND and three different E-proteins. Biochem. Biophys.

dHAND 和三种不同 E 蛋白之间的差异合作。

• 发表时间: 2004
• 期刊: Res. Commun. 323
• 作者: Isomoto H;Nakazato M;Ueno H;Date Y;Nishi Y;Mukae H;Mizuta Y;Ohtsuru A;Yamashita S;Kohno S;Murakami M;Murakami M
• 通讯作者: Murakami M

Overexpression of lectin-line oxidized low-density lipoprotein receptor-1 induces intramyocardial vasculopathy in apolipoprotein E-null mice.

凝集素线氧化低密度脂蛋白受体 1 的过度表达可诱导载脂蛋白 E 缺失小鼠发生心肌内血管病变。

• 发表时间: 2005
• 期刊: Circ. Res. 97
• 作者: Kojima;S.;et. al.;Yokoyama Y;Inoue K
• 通讯作者: Inoue K

Resistin-like molecule beta activates MAPKs, suppresses insulin signaling in hepatocytes, and induces diabetes, hyperlipidemia, and fatty liver in transgenic mice on a high fat diet.

抵抗素样分子β激活MAPK，抑制肝细胞中的胰岛素信号传导，并在高脂肪饮食的转基因小鼠中诱发糖尿病、高脂血症和脂肪肝。

• 发表时间: 2005
• 期刊: J.Biol.Chem. 280・51
• 作者: Viana AY;Sakoda H;et al.;Kushiyama A et al.
• 通讯作者: Kushiyama A et al.

Differential cooperation between dHAND and three different E-proteins.

dHAND 和三种不同 E 蛋白之间的差异合作。

• 发表时间: 2004
• 期刊: Biochem.Biophys.Res.Commun. 323
• 作者: Chu CP;Qiu DL;Kato K;Kunitake T;Watanabe S;Yu NS;Nakazato M;Kannan H.;Okuno M. et al.;Murakami M
• 通讯作者: Murakami M