Department of Neurosurgery, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8507, Japan.
Mech Dev. 2013 Sep-Oct;130(9-10):458-66. doi: 10.1016/j.mod.2013.07.001. Epub 2013 Jul 17.
The vascular system is the first organ to form in the developing mammalian embryo. The Notch signaling pathway is an evolutionarily conserved signaling mechanism essential for proper embryonic development in almost all vertebrate organs. The analysis of targeted mouse mutants has demonstrated essential roles of the Notch signaling pathway in embryonic vascular development. However, Notch signaling-deficient mice have so far not been examined in detail in the head region. The bHLH genes Hes1 and Hes5 are essential effectors for Notch signaling, which regulate the maintenance of progenitor cells and the timing of their differentiation in various tissues and organs. Here, we report that endothelial-specific Hes1 and Hes5 mutant embryos exhibited defective vascular remodeling in the brain. In addition, arterial identity of endothelial cells was partially lost in the brain of these mutant mice. These data suggest that Hes1 and Hes5 regulate vascular remodeling and arterial fate specification of endothelial cells in the development of the brain. Hes1 and Hes5 represent critical transducers of Notch signals in brain vascular development.
血管系统是在发育中的哺乳动物胚胎中首先形成的器官。Notch 信号通路是一种进化上保守的信号机制，对于几乎所有脊椎动物器官的正常胚胎发育都是必不可少的。对靶向敲除小鼠的分析表明 Notch 信号通路在胚胎血管发育中具有重要作用。然而，到目前为止， Notch 信号缺失的小鼠在头部区域还没有被详细研究。bHLH 基因 Hes1 和 Hes5 是 Notch 信号的必需效应因子，它们调节各种组织和器官中祖细胞的维持和分化的时机。在这里，我们报告内皮细胞特异性的 Hes1 和 Hes5 突变胚胎在大脑中表现出血管重塑缺陷。此外，这些突变小鼠大脑中的内皮细胞的动脉特性部分丧失。这些数据表明 Hes1 和 Hes5 调节大脑发育过程中血管重塑和内皮细胞的动脉命运特化。Hes1 和 Hes5 是脑血管发育中 Notch 信号的关键转导因子。
