Retrovirally transduced NCAM140 facilitates neuronal fate choice of hippocampal progenitor cells
Retrovirally transduced NCAM140 facilitates neuronal fate choice of hippocampal progenitor cells
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DOI：
10.1111/j.1471-4159.2005.03208.x
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发表时间：
2005-07-01
影响因子：
4.7
通讯作者：
Son, H
中科院分区：
文献类型：
--
作者：
Kim, JH;Lee, JH;Son, H
神经细胞粘附分子（NCAM）影响神经元细胞的增殖和分化。然而，人们对 NCAM 信号传导的下游影响知之甚少，例如与细胞命运选择相关的基因转录的改变。为了检查 NCAM 是否在海马神经发生过程中的细胞命运选择中发挥作用，我们使用包含全长 NCAM140 cDNA 和标记基因 EGFP 的逆转录病毒载体进行了功能获得研究，发现 NCAM140 通过激活原神经转录激活剂并同时抑制胶质细胞生成来促进神经发生。用丝裂原激活蛋白激酶激酶 (MEK) 抑制剂 PD098059 处理细胞，可下调 NCAM140 转导细胞中原神经转录因子的转录水平。总的来说，这些发现表明 NCAM140 可能通过细胞外信号调节激酶 (ERK) 依赖性方式调节原神经转录因子来促进海马神经发生。
Neural cell adhesion molecule (NCAM) influences proliferation and differentiation of neuronal cells. However, only a little is known about the downstream effects of NCAM signalling, such as alterations in gene transcription, which are associated with cell fate choice. To examine whether NCAM plays a role in cell fate choice during hippocampal neurogenesis, we performed a gain-of-function study, using a retroviral vector which contained full-length NCAM140 cDNA and the marker gene EGFP, and found that NCAM140 promoted neurogenesis by activating proneural transcription activators with concurrent inhibition of gliogenesis. The enhanced transcript levels of proneural transcription factors in NCAM140-transduced cells were down-regulated by treatment of the cells with mitogen-activated protein kinase kinase (MEK) inhibitor PD098059. Overall, these findings suggest that NCAM140 may facilitate hippocampal neurogenesis via regulation of proneurogenic transcription factors in an extracellular signal-regulated kinase (ERK)-dependent manner.