Repulsive and attractive semaphorins cooperate to direct the navigation of cardiac neural crest cells
Repulsive and attractive semaphorins cooperate to direct the navigation of cardiac neural crest cells
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DOI：
10.1016/j.ydbio.2008.06.028
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发表时间：
2008-09-01
影响因子：
2.7
通讯作者：
Kikutani, Hitoshi
中科院分区：
文献类型：
--
作者：
Toyofuku, Toshihiko;Yoshida, Junko;Kikutani, Hitoshi
心脏神经嵴是神经嵴的一个亚群，在发育过程中参与心脏流出道的形成。然而，它如何遵循定义的远程迁移途径仍不清楚。我们在这里发现迁移的心脏神经嵴细胞（NCCs）表达丛蛋白a2、丛蛋白d1和神经匹林。Plexin-A2的膜结合配体，信号素（Sema）6A和Sema6B，在背神经管和侧咽弓间质（NCC“途径”）中表达。Sema3C是Plexin-D1/neuropilin-1的配体，在心脏流出道（NCC“靶”）中表达。Sema6A和Sema6B排斥神经嵴细胞，而Sema3C吸引神经嵴细胞。在NCCs中，当Plexin-A2和Neuropilin-1或Plexin-D1分别被敲低时，Sema6A和Sema6B的斥力和Sema3C的吸引力减弱。当RNAi敲除减少NCCs中的每个受体时，NCCs不能在发育中的鸡胚胎中迁移到心脏流出道。此外，丛蛋白a2缺陷小鼠表现出心脏流出道形成缺陷。因此，我们得出结论，Sema6A/Sema6B通过Plexin-A2提供的排斥信号与Sema3C通过Plexin-D1提供的吸引信号的协调对于迁移的心脏ncc的精确导航是必需的。(C) 2008爱思唯尔公司版权所有。
The Cardiac neural crest, a subpopulation of the neural Crest, contributes to the cardiac Outflow tract formation during development. However, how it follows the defined long-range migratory pathway remains unclear. We show here that the migrating cardiac neural crest cells (NCCs) express Plexin-A2, Plexin-D1 and Neuropilin. The membrane-bound ligands for Plexin-A2, Semaphorin (Sema)6A and Sema6B, are expressed in the dorsal neural tube and the lateral pharyngeal arch mesenchyme (the NCC "routes"). Sema3C, a ligand for Plexin-D1/neuropilin-1, is expressed in the cardiac outflow tract (the NCC "target"). Sema6A and Sema6B repel neural crest cells, while Sema3C attracts neural crest cells. Sema6A and Sema6B repulsion and Sema3C attraction are diminished either when Plexin-A2 and Neuropilin-1, or When Plexin-D1, respectively, are knocked down in NCCs. When RNAi knockdown diminishes each receptor in NCCs, the NCCs fail to migrate into the Cardiac Outflow tract in the developing chick embryo. Furthermore, Plexin-A2-deficient mice exhibit defects of cardiac outflow tract formation. We therefore conclude that the coordination Of repulsive cues provided by Sema6A/Sema6B through Plexin-A2 paired with the attractive cue by Sema3C through Plexin-D1 is required for the precise navigation of migrating cardiac NCCs. (C) 2008 Elsevier Inc. All rights reserved.