Convergence of Notch and beta-catenin signaling induces arterial fate in vascular progenitors.
Convergence of Notch and beta-catenin signaling induces arterial fate in vascular progenitors.
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DOI：
10.1083/jcb.200904114
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发表时间：
2010-04-19
期刊：
影响因子：
--
通讯作者：
Yamashita JK
中科院分区：
文献类型：
--
作者：
Yamamizu K;Matsunaga T;Uosaki H;Fukushima H;Katayama S;Hiraoka-Kanie M;Mitani K;Yamashita JK
Notch胞内结构域和β-catenin与RBP-J共同调控基因转录，促进动脉内皮细胞的发育。控制动-静脉规范的分子机制尚未完全阐明。在此之前，我们建立了一个胚胎干细胞分化系统，并证明了cAMP信号和VEGF的激活可诱导Flk1+血管祖细胞的动脉内皮细胞（ECs）。在这里，我们展示了由Notch和β-catenin信号调节的新的动脉规范机制。Notch和gsk3 β介导的β-catenin信号通过磷脂酰肌醇-3激酶在cAMP下游被激活。VEGF强制激活Notch和β-catenin完全重建了camp诱导的动脉EC诱导，并协同增强了体外靶基因启动子活性和体内血管生成过程中动脉基因表达。在动脉内皮细胞中，在动脉基因的RBP-J结合位点上形成了一种与RBP-J、Notch细胞内结构域和β-catenin结合的蛋白复合物，而在静脉内皮细胞中则没有。这种动脉规范的分子机制导致对血管信号的综合和更全面的理解。
The Notch intracellular domain and β-catenin team up with RBP-J to regulate gene transcription and promote the development of arterial endothelial cells. Molecular mechanisms controlling arterial–venous specification have not been fully elucidated. Previously, we established an embryonic stem cell differentiation system and demonstrated that activation of cAMP signaling together with VEGF induces arterial endothelial cells (ECs) from Flk1+ vascular progenitor cells. Here, we show novel arterial specification machinery regulated by Notch and β-catenin signaling. Notch and GSK3β-mediated β-catenin signaling were activated downstream of cAMP through phosphatidylinositol-3 kinase. Forced activation of Notch and β-catenin with VEGF completely reconstituted cAMP-elicited arterial EC induction, and synergistically enhanced target gene promoter activity in vitro and arterial gene expression during in vivo angiogenesis. A protein complex with RBP-J, the intracellular domain of Notch, and β-catenin was formed on RBP-J binding sites of arterial genes in arterial, but not venous ECs. This molecular machinery for arterial specification leads to an integrated and more comprehensive understanding of vascular signaling.
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影响因子：
5.8
作者：
Mayor, C;Brudno, M;Dubchak, I
通讯作者：
Dubchak, I
DOI：
10.1242/dev.01724
发表时间：
2005-04
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Hayward P;Brennan K;Sanders P;Balayo T;DasGupta R;Perrimon N;Martinez Arias A
通讯作者：
Martinez Arias A
影响因子：
11.8
作者：
Grego-Bessa, Joaquin;Luna-Zurita, Luis;de la Pompa, Jose Luis
通讯作者：
de la Pompa, Jose Luis
影响因子：
9.2
作者：
Orsulic, S;Peifer, M
通讯作者：
Peifer, M
影响因子：
10.5
作者：
Adams, RH;Wilkinson, GA;Klein, R
通讯作者：
Klein, R