Endothelial expression of TGFβ type II receptor is required to maintain vascular integrity during postnatal development of the central nervous system.
Endothelial expression of TGFβ type II receptor is required to maintain vascular integrity during postnatal development of the central nervous system.
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DOI：
10.1371/journal.pone.0039336
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Arthur HM
中科院分区：
文献类型：
--
作者：
Allinson KR;Lee HS;Fruttiger M;McCarty JH;Arthur HM
内皮细胞中的tgf - β信号对于早期胚胎发育中的血管生成很重要，但对其在出生后早期生命中的作用知之甚少。为了解决这个问题，我们在新生小鼠中使用了他莫昔芬诱导的Cre-LoxP策略来特异性地消耗内皮细胞中的ii型TGFβ受体（Tgfbr2）。这导致多发微出血，肾小球样血管簇遍布大脑皮层和下丘脑以及视网膜组织。对这些突变体视网膜缺陷的详细检查显示，内皮粘附和紧密连接到位，周细胞被招募，血管平滑肌分化没有失败。然而，在这些突变体中，更深的视网膜丛未能形成，血管新生芽在向内核层发展的过程中停滞不前。相反，前导内皮细胞与相关的平滑肌细胞形成肾小球簇。这一证据表明，TGFβ信号不是血管成熟所必需的，但对于内皮细胞开始进入视网膜深层时的有组织迁移是必不可少的。因此，tgf - β信号在血管内皮细胞中至关重要，因为它在出生后早期迁移到发育中的神经组织中，维持血管生成前沿的血管完整性。
TGFβ signalling in endothelial cells is important for angiogenesis in early embryonic development, but little is known about its role in early postnatal life. To address this we used a tamoxifen inducible Cre-LoxP strategy in neonatal mice to deplete the TypeII TGFβ receptor (Tgfbr2) specifically in endothelial cells. This resulted in multiple micro-haemorrhages, and glomeruloid-like vascular tufts throughout the cerebral cortices and hypothalamus of the brain as well as in retinal tissues. A detailed examination of the retinal defects in these mutants revealed that endothelial adherens and tight junctions were in place, pericytes were recruited and there was no failure of vascular smooth muscle differentiation. However, the deeper retinal plexus failed to form in these mutants and the angiogenic sprouts stalled in their progress towards the inner nuclear layer. Instead the leading endothelial cells formed glomerular tufts with associated smooth muscle cells. This evidence suggests that TGFβ signalling is not required for vessel maturation, but is essential for the organised migration of endothelial cells as they begin to enter the deeper layers of the retina. Thus, TGFβ signalling is essential in vascular endothelial cells for maintaining vascular integrity at the angiogenic front as it migrates into developing neural tissues in early postnatal life.
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影响因子：
20.3
作者：
Levéen, P;Larsson, J;Karlsson, S
通讯作者：
Karlsson, S
DOI：
10.1073/pnas.1019761108
发表时间：
2011-02-15
影响因子：
11.1
作者：
Anderson, Keith D.;Pan, Li;Gale, Nicholas W.
通讯作者：
Gale, Nicholas W.
影响因子：
9.8
作者：
Chen, Jing;Smith, Lois E. H.
通讯作者：
Smith, Lois E. H.
DOI：
10.1523/jneurosci.5648-11.2012
发表时间：
2012-01-25
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Arnold TD;Ferrero GM;Qiu H;Phan IT;Akhurst RJ;Huang EJ;Reichardt LF
通讯作者：
Reichardt LF
Wnt/β-catenin信号传导控制血脑屏障的发展。
影响因子：
7.8
作者：
Liebner, Stefan;Corada, Monica;Bangsow, Thorsten;Babbage, Jane;Taddei, Andrea;Czupalla, Cathrin J.;Reis, Marco;Felici, Angelina;Wolburg, Hartwig;Fruttiger, Marcus;Taketo, Makoto M.;von Melchner, Harald;Plate, Karl Heinz;Gerhardt, Holger;Dejana, Elisabetta
通讯作者：
Dejana, Elisabetta