CHL1 negatively regulates the proliferation and neuronal differentiation of neural progenitor cells through activation of the ERK1/2 MAPK pathway
CHL1 negatively regulates the proliferation and neuronal differentiation of neural progenitor cells through activation of the ERK1/2 MAPK pathway
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DOI：
10.1016/j.mcn.2010.09.013
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发表时间：
2011-01-11
影响因子：
3.5
通讯作者：
Fan, Ming
中科院分区：
文献类型：
--
作者：
Huang, Xin;Zhu, Ling-ling;Fan, Ming
免疫球蛋白超家族的神经识别分子在神经系统的发育和再生中发挥着重要作用。 L1 的紧密同源物 (CHL1) 是 L1 识别分子家族的成员，在神经元发育过程中表达，表明其在神经祖细胞 (NPC) 中具有潜在作用。在这里，我们在体内和体外研究了CHL1在NPC增殖和分化中的作用及其可能的机制。与 CHL1+/+ 小鼠相比，CHL1-/- 小鼠脑室下区 (SVZ) 的 BrdU 阳性细胞数量显着增加。此外，CHL1-/- 小鼠的皮质板区域比 CHL1+/+ 对照小鼠有更多的 Tuj1 阳性细胞。进一步探讨CHL1在NPCs增殖和分化中的功能。来自 CHL1-/- 小鼠与同窝野生型小鼠的 NPC 被分离并在体外培养。与 CHL1+/+ 小鼠相比，源自 CHL1-/- 小鼠的 NPC 显示出更高的增殖和自我更新能力。在分化的过程中。 CHL1 缺乏在缺乏生长因子的情况下增强了神经元分化。此外，CHL1缺陷对NPC增殖的影响伴随着ERK1/2丝裂原激活蛋白激酶(MAPK)激活的增强，ERK1/2 MAPK的抑制剂消除了CHL1缺陷对NPC增殖的影响。我们的结果首先描述了 CHL1/ERK1/2 MAPK 信号传导对 NPC 增殖和神经元分化的负调节。 (C) 2010 Elsevier Inc. 保留所有权利。
Neural recognition molecules of the immunoglobulin superfamily play important roles in the development and regeneration of nervous system. Close Homologue of L1 (CHL1) is a member of the L1 family of recognition molecules which are expressed during neuronal development, suggesting a potential role in neural progenitor cells (NPCs). Here, we investigated the role of CHL1 in the proliferation and differentiation of NPCs both in vivo and in vitro, and the possible mechanism involved. The number of BrdU-positive cells in the subventricular zone (SVZ) significantly increased in CHL1-/- mice compared with CHL1+/+ mice. Moreover, there were more Tuj1-positive cells in the cortical plate region in CHL1-/- mice than in CHL1+/+ controls. To further examine the function of CHL1 in the proliferation and differentiation of NPCs. NPCs from CHL1-/- mice versus littermate wild-type mice were isolated and cultured in vitro. NPCs derived from CHL1-/- mice showed increased proliferation and self-renewal ability compared with CHL1+/+ mice. In the course of differentiation. CHL1 deficiency enhanced neuronal differentiation in the absence of growth factors. Furthermore, CHL1 deficiency on the proliferation of NPCs is accompanied by means of enhanced activation of ERK1/2 mitogen-activated protein kinase (MAPK) and the inhibitor of ERK1/2 MAPK eliminates the effect of CHL1 deficiency on the proliferation of NPCs. Our results first describe the negative modulation of the proliferation and neuronal differentiation of NPCs by CHL1/ERK1/2 MAPK signaling. (C) 2010 Elsevier Inc. All rights reserved.