Regulation of pre-natal circle of Willis assembly by vascular smooth muscle Notch signaling.
Regulation of pre-natal circle of Willis assembly by vascular smooth muscle Notch signaling.
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DOI：
10.1016/j.ydbio.2013.06.007
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发表时间：
2013-09-01
影响因子：
2.7
通讯作者：
Proweller, Aaron
中科院分区：
文献类型：
--
作者：
Yang, Ke;Banerjee, Suhanti;Proweller, Aaron
Willis环（cW）是大脑内连接半球循环的主要动脉侧支结构，在人类中，cW的解剖变异与中风风险有关。我们先前在血管平滑肌细胞（vSMC）Notch信号传导缺陷的成年小鼠中的研究揭示了动脉成熟和模式的改变，包括类似于人类变体的解剖学上不合格的cW。然而，在该模型中，cW形成对Notch信号传导的发育依赖性仍然没有表征。通过时空胚胎分析，我们现在证明，cW组装是一个出生前的过程高度敏感的vSMC Notch信号，其缺乏导致延迟新生血管丛的形成和欠发达的cW，包括关键的前交通动脉（AComA）互连前脑循环。突变胚胎还具有vSMC覆盖减少、口径不均匀和主要近端脑动脉分叉处的不对称分支的特征。在细胞水平上，尽管存在Vegfa，但血管内皮细胞增殖的显著减少存在于AComA组装区域中。此外，发育中的脑血管中Notch信号缺陷的vSMC具有Pdgfrβ和Jagged 1水平降低和增殖受损的特征。这些在胚胎脑中的集体发现支持了成年动物中的研究，证明了依赖于完整的vSMC Notch信号传导来对血管生成刺激进行最佳的新生血管反应。重要的是，新数据提供了对cW天然形成的独特见解，并强调了vSMC Notch信号在调节临床相关cW时空组装中的开拓性发育作用。
The circle of Willis (cW) is a major arterial collateral structure interconnecting hemispheric circulation within the brain, and in humans, anatomical variation of the cW is linked to stroke risk. Our prior studies in adult mice deficient in vascular smooth muscle cell (vSMC) Notch signaling revealed altered cerebroarterial maturation and patterning, including an anatomically incompetent cW similar to human variants. However, a developmental dependency on Notch signaling for cW formation in this model remained uncharacterized. Through temporospatial embryonic analyses, we now demonstrate that cW assembly is a pre-natal process highly sensitive to vSMC Notch signals, whose absence results in delayed nascent vascular plexus formation and under-development of the cW including the key anterior communicating artery (AComA) interconnecting anterior forebrain circulation. Mutant embryos additionally feature reduced vSMC coverage, non-uniform calibers and asymmetric branching at bifurcations of the major proximal cerebral arteries. At the cellular level, a notable reduction in vascular endothelial cell proliferation exists in the region of AComA assembly despite the presence of Vegfa. Furthermore, Notch signaling-deficient vSMCs in developing cerebral vessels feature reduced Pdgfrβ and Jagged1 levels and impaired proliferation. These collective findings in the embryonic brain support studies in adult animals demonstrating a reliance on intact vSMC Notch signaling for optimal neovascular responses to angiogenic stimuli. Importantly, the new data provide unique insights into the native formation of the cW and underscore a pioneering developmental role for vSMC Notch signaling in regulating temporospatial assembly of the clinically relevant cW.
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影响因子：
4.6
作者：
Hofmann, Jennifer J.;Zovein, Ann C.;Iruela-Arispe, M. Luisa
通讯作者：
Iruela-Arispe, M. Luisa
影响因子：
3.2
作者：
Kurz, Haymo
通讯作者：
Kurz, Haymo
影响因子：
5
作者：
Chalothorn D;Faber JE
通讯作者：
Faber JE
DOI：
10.1161/atvbaha.109.186890
发表时间：
2009-07
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Morrow D;Cullen JP;Liu W;Guha S;Sweeney C;Birney YA;Collins N;Walls D;Redmond EM;Cahill PA
通讯作者：
Cahill PA
影响因子：
64.5
作者：
Benedito, Rui;Roca, Cristina;Adams, Ralf H.
通讯作者：
Adams, Ralf H.