A distinct mechanism of vascular lumen formation in Xenopus requires EGFL7.
A distinct mechanism of vascular lumen formation in Xenopus requires EGFL7.
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DOI：
10.1371/journal.pone.0116086
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Conlon FL
中科院分区：
文献类型：
--
作者：
Charpentier MS;Tandon P;Trincot CE;Koutleva EK;Conlon FL
在脊椎动物血管发育过程中，管腔形成是内皮细胞束向功能管状血管转变的关键过程。在这里，我们使用爪蟾胚胎来探索背主动脉和后主静脉（在生命最初48小时内通过血管发生而产生的主要血管）管腔形成的细胞和分子机制。我们证明，内皮细胞最初通过形成表达ZO-1的紧密连接而彼此密切相关。血管管腔形成的特点是内皮细胞形状延长，连接从脐带中心向血管外周重组，紧密连接内开始表达Claudin-5。此外，与大多数脊椎动物的血管表现出特殊的顶端和基部结构域不同，我们发现早期非洲爪蟾的血管并没有极化。此外，我们证明，在胚胎中缺乏细胞外基质因子表皮生长因子样结构域7 (EGFL7)，这是一种与脊椎动物血管发育相关的进化保守因子，血管管腔无法形成。虽然Claudin-5能够及时定位于egfl7缺失胚胎的内皮紧密连接，但主动脉和静脉内皮细胞在细胞-细胞接触过程中不能发生适当的细胞形态变化或清晰的连接。综上所述，我们首次证明了非洲爪蟾主要血管内产生管腔的机制，并暗示EGFL7参与调节细胞形状和细胞间连接，以驱动适当的管腔形态发生。
During vertebrate blood vessel development, lumen formation is the critical process by which cords of endothelial cells transition into functional tubular vessels. Here, we use Xenopus embryos to explore the cellular and molecular mechanisms underlying lumen formation of the dorsal aorta and the posterior cardinal veins, the primary major vessels that arise via vasculogenesis within the first 48 hours of life. We demonstrate that endothelial cells are initially found in close association with one another through the formation of tight junctions expressing ZO-1. The emergence of vascular lumens is characterized by elongation of endothelial cell shape, reorganization of junctions away from the cord center to the periphery of the vessel, and onset of Claudin-5 expression within tight junctions. Furthermore, unlike most vertebrate vessels that exhibit specialized apical and basal domains, we show that early Xenopus vessels are not polarized. Moreover, we demonstrate that in embryos depleted of the extracellular matrix factor Epidermal Growth Factor-Like Domain 7 (EGFL7), an evolutionarily conserved factor associated with vertebrate vessel development, vascular lumens fail to form. While Claudin-5 localizes to endothelial tight junctions of EGFL7-depleted embryos in a timely manner, endothelial cells of the aorta and veins fail to undergo appropriate cell shape changes or clear junctions from the cell-cell contact. Taken together, we demonstrate for the first time the mechanisms by which lumens are generated within the major vessels in Xenopus and implicate EGFL7 in modulating cell shape and cell-cell junctions to drive proper lumen morphogenesis.
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影响因子：
2.7
作者：
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通讯作者：
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DOI：
10.1073/pnas.0808698106
发表时间：
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