Emerging pulmonary vasculature lacks fate specification.
Emerging pulmonary vasculature lacks fate specification.
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DOI：
10.1152/ajplung.90452.2008
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发表时间：
2009
期刊：
影响因子：
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通讯作者：
M. Schwarz;L. Caldwell;D. Cafasso;Haihua Zheng
中科院分区：
文献类型：
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作者：
M. Schwarz;L. Caldwell;D. Cafasso;Haihua Zheng
肺形态发生需要分支形态发生和血管化之间的精确协调，以产生能够在细胞-细胞界面支持呼吸的远端气道。然而，最初在肺中形成的血管的具体起源和类型仍然不清楚。在此，我们明确表明，在肺发育的早期阶段[即，胚胎（E）11.5天]，充满血流的功能性血管仅限于上皮远端的间充质。然而，到E14.5天，并且响应于上皮来源的VEGF信号，功能性血管从间充质延伸到上皮界面。此外，这些血管邻近多能间充质基质细胞，可能在此过程中发挥调节作用。与全身脉管系统一样且不同的是，EphrinB 2和EphB 4的免疫染色揭示了在紧急肺脉管系统中动脉和静脉身份是不可区分的。总的来说，这项研究提供的证据表明，肺血管化最初起源于间充质，远端的上皮细胞，动脉-静脉规格不存在于早期肺。在一个机制的水平上，我们表明，基底上皮VEGF提示内皮细胞向上皮细胞，他们在增殖，小管阶段进行形态发生。因此，我们的研究结果挑战现有的概念血管起源和身份在发展过程中。
Lung morphogenesis requires precise coordination between branching morphogenesis and vascularization to generate distal airways capable of supporting respiration at the cell-cell interface. The specific origins and types of blood vessels that initially form in the lung, however, remain obscure. Herein, we definitively show that during the early phases of lung development [i.e., embryonic day (E) 11.5], functional vessels, replete with blood flow, are restricted to the mesenchyme, distal to the epithelium. However, by day E14.5, and in response to epithelial-derived VEGF signals, functional vessels extend from the mesenchyme to the epithelial interface. Moreover, these vessels reside adjacent to multipotent mesenchymal stromal cells that likely play a regulatory role in this process. As well as and distinct from the systemic vasculature, immunostaining for EphrinB2 and EphB4 revealed that arterial and venous identity is not distinguishable in emergent pulmonary vasculature. Collectively, this study provides evidence that lung vascularization initially originates in the mesenchyme, distal to the epithelium, and that arterial-venous specification does not exist in the early lung. At a mechanistic level, we show that basilar epithelial VEGF prompts endothelial cells to move toward the epithelium where they undergo morphogenesis during the proliferative, canalicular stage. Thus our findings challenge existing notions of vascular origin and identity during development.