An anteroposterior wave of vascular inhibitor downregulation signals aortae fusion along the embryonic midline axis
An anteroposterior wave of vascular inhibitor downregulation signals aortae fusion along the embryonic midline axis
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DOI：
10.1242/dev.051664
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发表时间：
2010-11-01
期刊：
影响因子：
4.6
通讯作者：
Mikawa, Takashi
中科院分区：
文献类型：
--
作者：
Garriock, Robert J.;Czeisler, Catherine;Mikawa, Takashi
旁分泌信号，无论是积极的还是消极的，调节胚胎血管的定位和重塑。在哺乳动物和鸟类的胚胎中，第一个主要的重塑事件是两侧背主动脉在中线融合形成背主动脉。尽管背主动脉最初的双侧性是由脊索从中线分泌的抑制因子(BMP信号拮抗剂)所致，但尚不清楚融合后来是如何发出信号的。在这里，我们报告背主动脉融合受到脊索沿前后轴的信号变化的严格调控。在主动脉融合过程中，脊索不再对血管形成产生负面影响。这是通过转录下调负调控因子实现的，而正调控因子则维持在融合前的水平。特别是，脊索融合前在脊索表达最丰富的BMP拮抗剂Chordin在前后波中经历了戏剧性的下调。随着抑制信号的减弱和阳性因子SHH和VEGF在中线的持续表达，背主动脉融合是信号。这些结果证明了一种新的机制，通过调节血管抑制剂可以发生重大的血管模式改变，而不会改变正向血管调节因子的水平。
Paracrine signals, both positive and negative, regulate the positioning and remodeling of embryonic blood vessels. In the embryos of mammals and birds, the first major remodeling event is the fusion of bilateral dorsal aortae at the midline to form the dorsal aorta. Although the original bilaterality of the dorsal aortae occurs as the result of inhibitory factors (antagonists of BMP signaling) secreted from the midline by the notochord, it is unknown how fusion is later signaled. Here, we report that dorsal aortae fusion is tightly regulated by a change in signaling by the notochord along the anteroposterior axis. During aortae fusion, the notochord ceases to exert its negative influence on vessel formation. This is achieved by a transcriptional downregulation of negative regulators while positive regulators are maintained at pre-fusion levels. In particular, Chordin, the most abundant BMP antagonist expressed in the notochord prior to fusion, undergoes a dramatic downregulation in an anterior to posterior wave. With inhibitory signals diminished and sustained expression of the positive factors SHH and VEGF at the midline, fusion of the dorsal aortae is signaled. These results demonstrate a novel mechanism by which major modifications of the vascular pattern can occur through modulation of vascular inhibitors without changes in the levels of positive vascular regulators.