Impaired Hippocampal Neurogenesis and Vascular Formation in Ephrin-A5-Deficient Mice
Impaired Hippocampal Neurogenesis and Vascular Formation in Ephrin-A5-Deficient Mice
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DOI：
10.1002/stem.427
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发表时间：
2010-05-01
期刊：
影响因子：
5.2
通讯作者：
Osumi, Noriko
中科院分区：
文献类型：
--
作者：
Hara, Yoshinobu;Nomura, Tadashi;Osumi, Noriko
神经发生发生在哺乳动物大脑的整个生命周期中。海马齿状回（DG）是成体神经发生的主要区域之一，神经干/祖细胞不断产生新的颗粒神经元，尽管新生神经元产生和维持的分子机制仍然难以捉摸。在这里，我们发现肝配蛋白-A5（Eph 受体酪氨酸激酶的配体）在成人海马的神经发生和血管形成中发挥多种作用。在缺乏肝配蛋白-A5 功能的小鼠中，海马 DG 中的细胞增殖和新生神经元的存活严重降低。此外，肝配蛋白-A5 缺陷小鼠的血管内皮细胞中 EphA4 受体的分布发生改变，海马 DG 中的毛细血管变窄。因此，EphA/ephrin-A 信号传导在脑血管系统的建立和/或维持中发挥着至关重要的作用，作为成人神经源性生态位的重要组成部分。干细胞2010； 28：974-983
Neurogenesis occurs throughout the life in the mammalian brain. The hippocampal dentate gyrus (DG) is one of the major regions of the adult neurogenesis, where neural stem/progenitor cells continuously generate new granule neurons, although molecular mechanisms underlying generation and maintenance of newly born neurons are still elusive. Here we show that ephrin-A5, a ligand for Eph receptor tyrosine kinases, plays multiple roles in both neurogenesis and vascular formation in the adult hippocampus. In mice lacking ephrin-A5 function, cell proliferation and survival of newborn neurons were severely reduced in the hippocampus DG. Furthermore, ephrin-A5-deficient mice exhibited altered distribution of EphA4 receptor in the vascular endothelial cells and increased narrower capillaries in the hippocampus DG. EphA/ephrin-A signaling thus plays crucial roles in the establishment and/or maintenance of the brain vascular system, as an essential constituent of the adult neurogenic niche. STEM CELLS 2010; 28: 974-983