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

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如何影响细胞分化和器官发生，心血管和颅面发育是一个很好的模型。我们之前的研究表明，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组织的发育至关重要（Nature 368,703,1994）。在这项研究中，我们建立了ETAR敲入小鼠，其中感兴趣的基因可以通过重组酶介导的盒交换（RMCE）在ETAR启动子下表达，并使用该系统进行了如下分析。ETAR-/cETAR小鼠的ETAR-null表型完全恢复。心血管和颅面异常归一化，表明该RMCE系统在ETAR基因中功能良好。标记基因敲入ETAR+/lacZ小鼠的lacZ表达与原位杂交显示的ETAR mRNA表达基本一致。除神经嵴细胞外，其余细胞均表达ETAR。在in4中，就Gq/11介导的信号传导而言，ETAR被认为在很大程度上等同于ETBR。我们正在用Gq/11介导的信号来建立小鼠，其中etar无处不在地被激活

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