Dual roles of Sema6D in cardiac morphogenesis through region-specific association of its receptor, Plexin-A1, with off-track and vascular endothelial growth factor receptor type 2
Dual roles of Sema6D in cardiac morphogenesis through region-specific association of its receptor, Plexin-A1, with off-track and vascular endothelial growth factor receptor type 2
复制标题
DOI：
10.1101/gad.1167304
复制
发表时间：
2004-02-15
影响因子：
10.5
通讯作者：
Kikutani, H
中科院分区：
文献类型：
--
作者：
Toyofuku, T;Zhang, H;Kikutani, H
脑信号蛋白最初被认为是神经系统中的轴突导向因子，在器官发生中起着不可或缺的作用。在这里，我们证明了Sema 6D在心脏形态发生中的重要参与。在鸡胚发育过程中，Sema 6D的异位表达或针对Sema 6D的RNA干扰分别诱导心室腔扩大或缩小。Sema 6D还对心脏外植体发挥区域特异性活性，对来自圆锥动脉干节段的生长细胞发挥迁移促进活性，对来自心室的细胞发挥迁移抑制活性。丛状蛋白-A1作为主要的Sema 6D结合受体介导这些活性。丛状蛋白-A1与圆锥动脉干段中的血管内皮生长因子受体2型或心室段中的偏离轨道形成受体复合物;这些复合物负责Sema 6D对相应区域的影响。因此，丛状蛋白A1与其他受体成分的差异关联使得Sema 6D在相邻区域发挥不同的生物活性。这对于复杂的心脏形态发生至关重要。
Semaphorins, originally identified as axon guidance factors in the nervous system, play integral roles in organogenesis. Here, we demonstrate a critical involvement of Sema6D in cardiac morphogenesis. Ectopic expression of Sema6D or RNA interference against Sema6D induces expansion or narrowing of the ventricular chamber, respectively, during chick embryonic development. Sema6D also exerts region-specific activities on cardiac explants, a migration-promoting activity on outgrowing cells from the conotruncal segment, and a migration-inhibitory activity on those from the ventricle. Plexin-A1 mediates these activities as the major Sema6D-binding receptor. Plexin-A1 forms a receptor complex with vascular endothelial growth factor receptor type 2 in the conotruncal segment or with Off-track in the ventricle segment; these complexes are responsible for the effects of Sema6D on the respective regions. Thus, the differential association of Plexin-A1 with additional receptor components entitles Sema6D to exert distinct biological activities at adjacent regions. This is crucial for complex cardiac morphogenesis.