Mechanism for the involvement of the endothelin system in craniofacial and cardiovascular development

内皮素系统参与颅面和心血管发育的机制

• 批准号: 16590659
• 负责人: KURIHARA Yukiko
• 金额: $ 2.24万
• 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 (C)
• 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/en/grant/KAKENHI-PROJECT-16590659/
• 关键词: Neural crest cell; cardiovascular development; endothelin; endothelin A receptor; 鰓弓; 細胞内シグナル; エンドセリン-1; 頭部心臓神経堤細胞; 形態形成; ノックインマウス

We have demonstrated that the ET-1(endothelin-1) signal from branchial epithelium to mesenchyme is important to act on the ETAR(ETA receptor) expressed in the neural crest cells. This pathway regulates Dlx5/6 as homeotic gene which is down-steam of its pathway, and plays a role of dorso-ventral patterning in the 1st branchial arch. In other words, we have demonstrated that both dorsal and ventral 1st branchial arch is determined to be upper jaw pattern at the midgestation embryo, but only the ventral portion receives the ET-1-ETAR-Dlx5/6 signal to specify the lower pattern. Then we made the mice in which transgene can be knocked-in into the ETAR gene locus. For this purpose, mutant lox sequences were inserted into the ETAR gene locus to allow Cre recombinase-mediated cassette exchange. The phenotype of ETAR-mutant lox homozygotes are the same as the phenotype of ET-1 or ETAR homozygotes. We then knocked in the LacZ gene into the downstream of ETAR promoter in these mice. Consequently, target cells of the ET-1 signal contributed to branchial arch and cardiovascular development were visualized. These mice enable us to trace the process of cardiovascular development and to analyze of mutual interaction between neural crest cells and other cells. Further knock-in studies are expected to reveal the molecular mechanism underlying branchial arch and cardiovascular development.

我们已经证明，从鳃上皮到间充质的ET-1(ET-1)信号对神经脊细胞表达的ETAR(ETAR)具有重要作用。该途径调控同源异型基因Dlx5/6，Dlx5/6是其途径的下游，在第一鳃弓起背腹模式的作用。换句话说，我们已经证明，在中期胚胎中，背侧和腹侧的第一鳃弓都被确定为上颌型，但只有腹侧部分接收到ET-1-ETAR-Dlx5/6信号来指定下颌型。然后我们制造了转基因可以被敲入Etar基因座的小鼠。为此，突变的lox序列被插入到Etar基因位点，以允许Cre重组酶介导盒交换。Etar突变的lox纯合子的表型与ET-1或Etar纯合子的表型相同。然后，我们在这些小鼠的ETAR启动子下游插入了LacZ基因。因此，ET-1信号的靶细胞对颧弓和心血管发育的作用被可视化。这些小鼠使我们能够追踪心血管发育的过程，并分析神经脊细胞与其他细胞之间的相互作用。进一步的连锁研究有望揭示颧弓和心血管发育的分子机制。

项目成果

Idl gene transfer confers angiogenic property on fully differentiated endothelial cells and contributes to therapeutic angiogenesis.

Idl基因转移赋予完全分化的内皮细胞血管生成特性并有助于治疗性血管生成。

• 发表时间: 2005
• 期刊: Circulation 112
• 作者: Yoshimoto T;Hirata Y;Tsujita K.;Hayasaki T;Kaikita K;Nakayama M;Koga H;Otsuka F;Sakamoto T;Hayasaki T.;Kaikita K.;Nakayama M.;Koga H.;Otsuka F.;Sakamoto T.;Kaikita K;Nakayama M;Yamamuro M;Koga H.;Watanabe K.;Nishiyama K.;Yamamuro M.;Miyamoto S.;Koga H;Watanabe K;Nishiyama K
• 通讯作者: Nishiyama K

Transcriptional activity of Pax3 is co-activated by TAZ

• DOI: 10.1016/j.bbrc.2005.10.214
• 发表时间: 2006-01-13
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Murakami, M;Tominaga, J;Kurihara, H
• 通讯作者: Kurihara, H

Id1 Gene Transfer Confers Angiogenic Property on Fully Differentiated Endothelial Cells and Contributes to Therapeutic Angiogenesis

• DOI: 10.1161/circulationaha.104.516898
• 发表时间: 2005-11
• 期刊: Circulation
• 影响因子: 37.8
• 作者: Koichi Nishiyama;K. Takaji;Keiichiro Kataoka;Y. Kurihara;M. Yoshimura;A. Kato;H. Ogawa;H. Kurihara

Endothelin-1 regulates the dorsoventral branchial arch patterning in mice

• DOI: 10.1016/j.mod.2004.02.002
• 发表时间: 2004-04-01
• 期刊: MECHANISMS OF DEVELOPMENT
• 影响因子: 2.6
• 作者: Ozeki, H;Kurihara, Y;Kurihara, H
• 通讯作者: Kurihara, H

Temporal requirement of signaling cascade involving endotheling-1/endothelin A receptor in branchial arch development.

鳃弓发育中涉及内皮素 1/内皮素 A 受体的信号级联的时间要求。

• 发表时间: 2004
• 期刊: Mech.Dev. 121
• 作者: Motooka M;Koike H;Yokoyama T et al.;Takeishi Y.;Fukuhara S
• 通讯作者: Fukuhara S