Ece1 and Tbx1 define distinct pathways to aortic arch morphogenesis.
Ece1 and Tbx1 define distinct pathways to aortic arch morphogenesis.
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Ece1 和 Tbx1 定义了主动脉弓形态发生的不同途径。
DOI：
10.1002/dvdy.10358
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发表时间：
2003
期刊：
影响因子：
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通讯作者：
Baldini,Antonio
中科院分区：
文献类型：
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作者：
Morishima,Masae;Yanagisawa,Hiromi;Yanagisawa,Masashi;Baldini,Antonio
咽弓动脉（PAA）重塑缺陷占几例先天性心脏病。内皮素-1遗传通路或Tbx 1（DiGeorge综合征的候选基因）的突变可导致类似的主动脉弓缺损。以前的研究表明，Tbx 1可能会触发从咽弓的扩散信号，以支持的PAA，有助于成熟的主动脉弓的增长。Tbx 1和Fgf 8之间的遗传相互作用的演示指出FGF信号作为一个可能的候选人。由于Fgf 8与内皮素-1信号相互作用，并且由于内皮素-1信号与咽器中的神经嵴衍生细胞相互作用，我们假设Tbx 1和内皮素-1信号可能有助于主动脉弓形态发生所需的相同途径。因此，我们分析了内皮素转换酶（Ece 1）或Tbx 1基因突变和复合突变的小鼠。结果表明，这两个基因在PAAs的重塑中具有不同的作用，并且不相互作用。Tbx 1是PAA形成、早期生长和重塑所必需的，而Ece 1是颅弓动脉退行和最尾弓动脉生长所必需的。后一种功能可能与内皮素-1通路在神经嵴功能中的已知作用有关。Developmental Dynamics 228：95-104，2003.© 2003 Wiley利斯公司
Pharyngeal arch artery (PAA) remodeling defects account for several cases of congenital heart disease. Mutations in the Endothelin‐1 genetic pathway orTbx1, a candidate gene for DiGeorge syndrome, cause similar aortic arch defects. Previous research suggests that Tbx1 may trigger diffusible signals from the pharyngeal arches to support the growth of the PAAs that contribute to the mature aortic arch. The demonstration of genetic interaction betweenTbx1andFgf8pointed to FGF signaling as a possible candidate. BecauseFgf8interacts with Endothelin‐1 signaling and because Endothelin‐1 signaling interacts with neural crest‐derived cells in the pharyngeal apparatus, we hypothesized thatTbx1and Endothelin‐1 signaling may contribute to the same pathway required for aortic arch morphogenesis. Therefore, we have analyzed mice mutated for the endothelin converting enzyme (Ece1) orTbx1genes and compound mutants. Results show that the two genes have different roles in the remodeling of the PAAs and do not interact. We propose thatTbx1is required for the formation and early growth and remodeling of the PAAs, whereasEce1is necessary for regression of the cranial arch arteries and growth of the most caudal arch arteries. The latter function is likely related to the known role of the Endothelin‐1 pathway in neural crest function. Developmental Dynamics 228:95–104, 2003. © 2003 Wiley‐Liss, Inc.