Venous endothelin guides sympathetic innervation of the developing mouse heart.

Venous endothelin guides sympathetic innervation of the developing mouse heart.
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DOI:
10.1038/ncomms4918
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发表时间:
2014-05-29
影响因子:
16.6
通讯作者:
Makita, Takako
Makita, Takako
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Manousiouthakis, Eleana;Mendez, Monica;Garner, Madeline C.;Exertier, Prisca;Makita, Takako

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在器官发育过程中负责建立正确的靶神经支配的机制在很大程度上是未知的。交感神经穿过或跟随血管到达它们的终末器官,这表明存在指导轴突延伸的血管引导线索。心脏的窦房结和心室接受来自星状神经节(STG)的交感神经支配。在这里,我们表明,STG轴突遵循静脉,特别是上级静脉腔和静脉窦,以达到这些目标。我们发现,这些路线的选举是由静脉内皮衍生的内皮素-1,通过其特异性受体Ednra内表达的STG神经元的亚群发挥作用。此外,我们证明了Edn 1-Ednra信号传导对于交感神经对心脏的功能调节至关重要。我们的研究结果目前静脉Edn 1作为交感神经的指导线索,并显示轴突的指导机制是如何与终末器官形态发生协调。
The mechanisms responsible for establishing correct target innervation during organ development are largely unknown. Sympathetic nerves traverse or follow blood vessels to reach their end-organs, suggesting the existence of vascular guidance cues that direct axonal extension. The sinoatrial node and the ventricle of the heart receive sympathetic innervation from the stellate ganglia (STG). Here we show that STG axons follow veins, specifically the superior vena cavae and sinus venosus, to reach these targets. We find that the election of these routes is determined by venous endothelium-derived endothelin-1, acting through its specific receptor Ednra expressed within a subpopulation of STG neurons. Furthermore, we demonstrate that Edn1-Ednra signaling is essential for functional regulation of the heart by sympathetic nerves. Our findings present venous Edn1 as a sympathetic guidance cue, and show how axon guidance mechanisms are coordinated with end-organ morphogenesis.
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