PlexinD1 and semaphorin signaling are required in endothelial cells for cadiovascular development
PlexinD1 and semaphorin signaling are required in endothelial cells for cadiovascular development
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DOI：
10.1016/j.devcel.2004.06.002
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发表时间：
2004-07-01
影响因子：
11.8
通讯作者：
Epstein, JA
中科院分区：
文献类型：
--
作者：
Gitler, AD;Lu, MM;Epstein, JA
识别对心脏形态发生至关重要的新信号通路将有助于我们了解先天性心脏病（CHD），先天性心脏病仍然是全世界新生儿死亡的主要原因。由信号蛋白配体和丛蛋白受体介导的信号有助于中枢神经系统中轴突的复杂模式。在这里，我们描述了一个相关的信号通路，涉及分泌的 3 类信号蛋白、神经毡蛋白和由内皮细胞表达的丛蛋白受体 PlexinD1。小鼠体内这条通路的中断会导致冠心病和血管模式缺陷。 PlexinD1失活引起的CHD类型先前被归因于神经嵴异常。在这里，我们证明这种形式的先心病可能是由细胞自主内皮缺陷引起的。因此，介导中枢神经系统轴突引导的分子程序也在内皮细胞中发挥作用，以协调心脏形态发生的关键方面。
The identification of new signaling pathways critical for cardiac morphogenesis will contribute to our understanding of congenital heart disease (CHD), which remains a leading cause of mortality in newborn children worldwide. Signals mediated by semaphorin Iigands and plexin receptors contribute to the intricate patterning of axons in the central nervous system. Here, we describe a related signaling pathway involving secreted class 3 semaphorins, neuropilins, and a plexin receptor, PlexinD1, expressed by endothelial cells. Interruption of this pathway in mice results in CHD and vascular patterning defects. The type of CHD caused by inactivation of PlexinD1 has previously been attributed to abnormalities of neural crest. Here, we show that this form of CHD can be caused by cell-autonomous endothelial defects. Thus, molecular programs that mediate axon guidance in the central nervous system also function in endothelial cells to orchestrate critical aspects of cardiac morphogenesis.