Inhibitor of DNA binding 2 promotes axonal growth through upregulation of Neurogenin2
Inhibitor of DNA binding 2 promotes axonal growth through upregulation of Neurogenin2
复制标题
DNA 结合抑制剂 2 通过上调 Neurogenin2 促进轴突生长。
DOI：
10.1016/j.expneurol.2019.112966
复制
发表时间：
2019-10-01
影响因子：
5.3
通讯作者：
Yu, Panpan
中科院分区：
文献类型：
--
作者：
Huang, Zhonghai;Liu, Jing;Yu, Panpan
操纵发育调控基因是一种很有前途的策略，以提高成人神经元的内在生长能力。DNA结合抑制因子2（Inhibitor of DNA binding 2，Id2）是bHLH转录因子的负调控因子，在有丝分裂后的神经元中强制表达，促进轴突生长。神经生成素2（Ngn 2）是一种神经特异性bHLH因子，其在发育期间控制神经元命运并驱动神经元分化。在这项研究中，我们研究了Id2促进轴突生长的机制，并揭示了Ngn 2有助于Id2在神经元中的生长激活作用。通过评估RNA和蛋白质水平，Ngn2表达随着Id2活性的增加而上调。Id2或Ngn 2在皮质神经元中的强制表达显著促进轴突生长，而对树突影响不大。此外，Ngn 2的敲低损害了Id2的轴突生长促进作用，这意味着Id2对轴突生长的作用依赖于Ngn 2。这些发现表明，神经元Ngn 2的升高可能是一种新的治疗策略，以刺激轴突再生。
Manipulation of developmentally regulated genes presents a promising strategy to enhance the intrinsic growth capability of adult neurons. Inhibitor of DNA binding 2 (Id2), a negative regulator of bHLH transcriptional factors, promotes axonal growth after its forced expression in post-mitotic neurons. Neurogenin2 (Ngn2) is a neural specific bHLH factor which controls neuronal fate and drives neuronal differentiation during development. In this study, we investigated the mechanism of Id2 in promoting axonal growth and revealed that Ngn2 contributed to the growth-activating role of Id2 in neurons. Ngn2 expression was upregulated with increased Id2 activity by assessing RNA and protein levels. Forced expression of Id2 or Ngn2 in cortical neurons significantly promoted axonal growth with little effect on dendrites. Furthermore, knockdown of Ngn2 impaired the axonal growth promoting effect of Id2, implying that the effect of Id2 on axonal growth depends on Ngn2. These findings suggest that elevation of neuronal Ngn2 may be a new therapeutic strategy to stimulate axonal regeneration.