Vascular Mural Cells Promote Noradrenergic Differentiation of Embryonic Sympathetic Neurons

Vascular Mural Cells Promote Noradrenergic Differentiation of Embryonic Sympathetic Neurons
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DOI:
10.1016/j.celrep.2015.05.028
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发表时间:
2015-06-23
期刊:
影响因子:
8.8
通讯作者:
Eichmann, Anne
Eichmann, Anne
中科院分区:
生物学1区
文献类型:
--
作者:
Fortuna, Vitor;Pardanaud, Luc;Eichmann, Anne

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交感神经系统控制心血管系统中的平滑肌张力和心率。节后交感神经元(SN)在背主动脉(DA)附近发育,并支配内脏平滑肌靶点。在这里,我们使用斑马鱼胚胎来询问DA是否是SN发育所必需的。我们发现,去甲肾上腺素(NA)分化的SN前体时间一致的血管壁细胞(VMC)招聘DA和血管成熟。阻断血管成熟抑制VMC募集并阻断SN前体的NA分化。血小板衍生生长因子受体(PDGFR)信号传导的抑制阻止VMC分化,也阻断SN前体的NA分化。NA分化在缺乏内皮细胞但具有VMC的钟形突变体中是正常的。因此,PDGFR介导的壁细胞募集介导主动脉和交感神经前体之间的神经血管相互作用,并促进其去甲肾上腺素能分化。
The sympathetic nervous system controls smooth muscle tone and heart rate in the cardiovascular system. Postganglionic sympathetic neurons (SNs) develop in close proximity to the dorsal aorta (DA) and innervate visceral smooth muscle targets. Here, we use the zebrafish embryo to ask whether the DA is required for SN development. We show that noradrenergic (NA) differentiation of SN precursors temporally coincides with vascular mural cell (VMC) recruitment to the DA and vascular maturation. Blocking vascular maturation inhibits VMC recruitment and blocks NA differentiation of SN precursors. Inhibition of platelet-derived growth factor receptor (PDGFR) signaling prevents VMC differentiation and also blocks NA differentiation of SN precursors. NA differentiation is normal in cloche mutants that are devoid of endothelial cells but have VMCs. Thus, PDGFR-mediated mural cell recruitment mediates neurovascular interactions between the aorta and sympathetic precursors and promotes their noradrenergic differentiation.