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Molecular mechanism for intercellular interactions involved in cardiovascular a〓craniofacial development

心血管颅面发育中细胞间相互作用的分子机制

基本信息

批准号：
18590802
负责人：
KURIHARA Yukiko
金额：
$ 2.57万
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：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590802/
关键词：
Endothelin Knock-In mouse Cardiovascular development Morphogenesis 神経堤細胞

项目摘要

Cardiovascular and craniofacial development in vertebrates is a complex process involving the coordinated interaction of different cell populations. To elucidate how cell-cell interactions operate cell differentiation and organogenesis, cardiovascular and craniofacial development serves as a good model. Our previous study has revealed that Endothelin-1/Endothelin A receptor (ETAR) signal was essential for cranial and cardiac neural crest cell-derived tissue development(Nature 368, 703, 1994). In this study, we have established ETAR knock-in mice in which genes of interested can be expressed under the ETAR promoter by recombinase mediated cassette exchange (RMCE), and have used this system for analysis as follows.1. Knock-in of ETAR cDNA The ETAR-null phenotype was completely rescued in ETAR-/cETAR mice. Cardiovascular and craniofacial abnormalities were normalized, suggesting that this RMCE system functioned well in the ETAR gene.2. Knock-in of marker genes The lacZ expression in ETAR+/lacZ mice almost recapitulates the expression of ETAR mRNA revealed by whole-mount in situ hybridization. Moreover, ETAR expressing cells except for neural crest cells were i3. Knock-in of ETAR-/ETBR ETAR has been considered to be largely equivalent to ETBR in terms of Gq/11-mediated signaling in in4. Knock-in of other genes We are establishing mice in terms of Gq/11-mediated signaling in which ETARs are ubiquitously activate

脊椎动物的心血管和颅面发育是一个复杂的过程，涉及不同细胞群的协调相互作用。为了阐明细胞间的相互作用是如何操作细胞分化和器官发生的，心血管和颅面发育是一个很好的模型。我们先前的研究已经揭示了内皮素-1/内皮素A受体（ETAR）信号对于颅和心脏神经嵴细胞衍生的组织发育是必需的（Nature 368，703，1994）。在本研究中，我们建立了ETAR基因敲入小鼠模型，通过重组酶介导的表达盒交换（RMCE）技术将目的基因在ETAR启动子下表达，并利用该系统进行了如下分析. ETAR cDNA的敲入ETAR-/cETAR小鼠中的ETAR-无效表型被完全挽救。心血管和颅面异常正常化，表明该RMCE系统在ETAR基因中功能良好。标记基因的敲入ETAR+/lacZ小鼠中的lacZ表达几乎重现了通过整体原位杂交揭示的ETAR mRNA的表达。此外，除神经嵴细胞外，ETAR表达细胞为i3。ETAR-/ETBR的敲入ETAR在in 4中的Gq/11介导的信号传导方面被认为在很大程度上等同于ETBR。我们正在建立Gq/11介导的信号转导小鼠，其中ETAR普遍被激活