Abnormal arterial-venous fusions and fate specification in mouse embryos lacking blood flow.
Abnormal arterial-venous fusions and fate specification in mouse embryos lacking blood flow.
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缺乏血流的小鼠胚胎的异常动静脉融合和命运规范。
DOI：
10.1038/s41598-017-12353-z
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发表时间：
2017
影响因子：
4.6
通讯作者：
Wang,RongA
中科院分区：
文献类型：
--
作者：
Hwa,JenniferJ;Beckouche,Nathan;Huang,Lawrence;Kram,Yoseph;Lindskog,Henrik;Wang,RongA
血流在哺乳动物动脉和静脉的形态发生中的功能还不清楚。我们研究了Ncx 1 −/−突变体的背主动脉（DA）和主静脉（CV）的发育，这些突变体由于缺乏在心脏中特异性表达的钠钙离子交换剂而缺乏血流。突变体DA和CV连接异常。Ncx 1 −/−突变DA的内皮缺乏动脉标记物ephrin-B2和Connexin-40的正常表达。Notch 1激活，已知促进动脉规格，减少突变DA内皮细胞（EC），异位表达静脉标记Coup-TFII。这些发现表明，流量在DA通过促进动脉和抑制静脉标记物表达的基本功能。相反，血流在CV中的作用较小，因为在Ncx 1 −/−突变体中，CV EC中动静脉标记物的表达没有受到显著影响。我们提出了一种分子机制，通过调节DA EC的动静脉特化，以确保发育中的DA和CV的适当分离，血流介导DA和CV形态发生。
The functions of blood flow in the morphogenesis of mammalian arteries and veins are not well understood. We examined the development of the dorsal aorta (DA) and the cardinal vein (CV) inNcx1−/−mutants, which lack blood flow due to a deficiency in a sodium calcium ion exchanger expressed specifically in the heart. The mutant DA and CV were abnormally connected. The endothelium of theNcx1−/−mutant DA lacked normal expression of the arterial markers ephrin-B2 and Connexin-40. Notch1 activation, known to promote arterial specification, was decreased in mutant DA endothelial cells (ECs), which ectopically expressed the venous marker Coup-TFII. These findings suggest that flow has essential functions in the DA by promoting arterial and suppressing venous marker expression. In contrast, flow plays a lesser role in the CV, because expression of arterial-venous markers in CV ECs was not as dramatically affected inNcx1−/−mutants. We propose a molecular mechanism by which blood flow mediates DA and CV morphogenesis, by regulating arterial-venous specification of DA ECs to ensure proper separation of the developing DA and CV.