A new role for the Endothelin-1/Endothelin-A receptor signaling during early neural crest specification
A new role for the Endothelin-1/Endothelin-A receptor signaling during early neural crest specification
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DOI：
10.1016/j.ydbio.2008.08.007
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发表时间：
2008-11-01
影响因子：
2.7
通讯作者：
Aybar, Manuel J.
中科院分区：
文献类型：
--
作者：
Bonano, Marcela;Tribulo, Celeste;Aybar, Manuel J.
神经嵴是由表皮、神经板和中胚层发出的信号在神经板的边缘诱导而成的。在这项工作中，我们第一次显示存在的神经嵴的维护步骤，这是依赖于从中胚层释放的信号。我们确定了内皮素-1（Edn 1）及其受体（Ednra）作为该信号的关键参与者，并且我们表明Edn 1/Ednra信号传导是通过细胞特化和细胞存活的双重机制维持神经嵴所必需的。我们证明：（i）Ednra在预期的神经嵴中表达;（ii）用反义吗啉代或用特异性化学抑制剂进行的功能丧失实验抑制了早期神经嵴标记物的表达;（iii）功能获得实验扩大了神经嵴区域;（iv）上位性实验表明Ednra/Edn 1位于早期神经嵴基因Msx 1的下游和晚期基因Sox 9和Sox 10的上游;和（v）Edn 1/Ednra信号传导抑制细胞凋亡并控制神经嵴的细胞特化。总之，我们的研究结果提供了一个新的作用Edn 1/Ednra细胞信号通路在早期神经嵴发育的见解。(C)2008年爱思唯尔公司All rights reserved.
The neural crest is induced at the border of the neural plate in a multistep process by signals emanated from the epidermis, neural plate and mesoderm. In this work we show for the first time the existence of a neural crest maintenance step which is dependent on signals released from the mesoderm. We identified Endothelin-1 (Edn1) and its receptor (Ednra) as key players of this signal and we show that Edn1/Ednra signaling is required for maintenance of the neural crest by a dual mechanism of cell specification and cell Survival. We show that: (i) Ednra is expressed in prospective neural crest; (ii) loss-of-function experiments with antisense morpholino or with specific chemical inhibitor suppress the expression of early neural crest markers; (iii) gain-of-function experiments expand the neural crest territory; (iv) epistatic experiments show that Ednra/Edn1 is downstream of the early neural crest gene Msx1 and upstream of the late genes Sox9 and Sox10; and (v) Edn1/Ednra signaling inhibits apoptosis and controls cell specification of the neural crest. Together, our results provide insight on a new role of Edn1/Ednra cell signaling pathway during early neural crest development. (C) 2008 Elsevier Inc. All rights reserved.