机构:[1]Guangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education Joint International Research Laboratory of CNS Regeneration, Jinan University, Guangzhou 510632, China [2] Norton Neuroscience Institute, Norton Healthcare, Louisville, KY 40202, USA [3]Department of Neurological Surgery, University of Louisville School of Medicine, Louisville, KY 40292, USA [4]Interdisciplinary Innovation Institute of Medicine and Engineering, Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China [5]Institute of Hypoxia Medicine, Xuanwu Hospital, Capital Medical University, Beijing 100053, China 首都医科大学宣武医院低氧医学研究室
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.
Copyright ? 2019 Elsevier Inc. All rights reserved.
基金:
This work
was supported by National Natural Science Foundation of China (No.
81601066); Natural Science Foundation of Guangdong Province (No.
2017A030313103 and 2016A030313096), China; Beijing Municipal
Natural Science Foundation (No. 7192103), China.
第一作者机构:[1]Guangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education Joint International Research Laboratory of CNS Regeneration, Jinan University, Guangzhou 510632, China
共同第一作者:
通讯作者:
通讯机构:[*1]Guangdong-Hongkong-Macau Institute of CNS Regeneration, Jinan University, 601 W. Huangpu Ave., Guangzhou 510632, China.[*2]School of Biological Science and Medical Engineering, Beihang University, No. 37 Xueyuan Road, Haidian District, Beijing 100191, China.
推荐引用方式(GB/T 7714):
Huang Zhonghai,Liu Jing,Jin Jingyu,et al.Inhibitor of DNA binding 2 promotes axonal growth through upregulation of Neurogenin2.[J].Experimental neurology.2019,320:112966.doi:10.1016/j.expneurol.2019.112966.
APA:
Huang Zhonghai,Liu Jing,Jin Jingyu,Chen Qingpei,Shields Lisa B E...&Yu Panpan.(2019).Inhibitor of DNA binding 2 promotes axonal growth through upregulation of Neurogenin2..Experimental neurology,320,
MLA:
Huang Zhonghai,et al."Inhibitor of DNA binding 2 promotes axonal growth through upregulation of Neurogenin2.".Experimental neurology 320.(2019):112966