title: Brain-specific ablation of Efr3a promotes adult hippocampal neurogenesisviathe brain-derived neurotrophic factor pathway.
abstract: Efr3 is a newly identified plasma membrane protein and plays an important role in the phosphoinositide metabolism on the plasma membrane. However, although it is highly expressed in the brain, the functional significance of Efr3 in the brain is not clear. In the present study, we generatedEfr3af/fmice and then crossed them withNestin-Cremice to delete Efr3a, one of the Efr3 isoforms, specifically in the brain. We found that brain-specific ablation of Efr3a promoted adult hippocampal neurogenesis by increasing survival and maturation of newborn neurons without affecting their dendritic tree morphology. Moreover, the brain-derived neurotrophic factor (BDNF)-tropomyosin-related kinase B (TrkB) signaling pathway was significantly enhanced in the hippocampus of Efr3a-deficient mice, as reflected by increased expression of BDNF, TrkB, and the downstream molecules, including phospho-MAPK and phospho-Akt. Furthermore, the number of TUNEL+cells was decreased in the subgranular zone of dentate gyrus in Efr3a-deficient mice compared with that of control mice. Our data suggest that brain-specific deletion of Efr3a could promote adult hippocampal neurogenesis, presumably by upregulating the expression of BDNF and its receptor, TrkB, and therefore provide new insight into the roles of Efr3 in the brain.-Qian, Q., Liu, Q., Zhou, D., Pan, H., Liu, Z., He, F., Ji, S., Wang, D., Bao, W., Liu, X., Liu, Z., Zhang, H., Zhang, X., Zhang, L., Wang, M., Xu, Y., Huang, F., Luo, B., Sun B. Brain-specific ablation of Efr3a promotes adult hippocampal neurogenesisviathe brain-derived neurotrophic factor pathway.
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology, Ministry of Health of China.|Key Laboratory of Neurobiology of Zhejiang Province, and.|Department of Neurology, First Affiliated Hospital, Collaborative Innovation Center for Brain Science, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Qian
authors.affiliation: Shanghai Advanced Research Institute, University of Chinese Academy of Sciences, Shanghai, China.
authors.forename: Qiuji
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology, Ministry of Health of China.|Key Laboratory of Neurobiology of Zhejiang Province, and.
authors.forename: Dongming
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology, Ministry of Health of China.|Key Laboratory of Neurobiology of Zhejiang Province, and.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Pan
authors.affiliation: Ministry of Education (MOE) Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing, China; and.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Neurology, First Affiliated Hospital, Collaborative Innovation Center for Brain Science, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Fangping
authors.initials: F
authors.lastname: He
authors.affiliation: Institute of Neuroscience, Shanghai Institute of Biological Science, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Suying
authors.initials: S
authors.lastname: Ji
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology, Ministry of Health of China.|Key Laboratory of Neurobiology of Zhejiang Province, and.
authors.forename: Dongpi
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Neurology, First Affiliated Hospital, Collaborative Innovation Center for Brain Science, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Wangxiao
authors.initials: W
authors.lastname: Bao
authors.forename: Xinyi
authors.initials: X
authors.lastname: Liu
authors.affiliation: Ministry of Education (MOE) Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing, China; and.
authors.forename: Zhaoling
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology, Ministry of Health of China.|Key Laboratory of Neurobiology of Zhejiang Province, and.
authors.forename: Heng
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology, Ministry of Health of China.|Key Laboratory of Neurobiology of Zhejiang Province, and.
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology, Ministry of Health of China.|Key Laboratory of Neurobiology of Zhejiang Province, and.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology, Ministry of Health of China.|Key Laboratory of Neurobiology of Zhejiang Province, and.
authors.forename: Mingkai
authors.initials: M
authors.lastname: Wang
authors.affiliation: Ministry of Education (MOE) Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing, China; and.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Shanghai Advanced Research Institute, University of Chinese Academy of Sciences, Shanghai, China; luobenyan@zju.edu.cn bsun@zju.edu.cn.
authors.forename: Fude
authors.initials: F
authors.lastname: Huang
authors.affiliation: Department of Neurology, First Affiliated Hospital, Collaborative Innovation Center for Brain Science, Zhejiang University School of Medicine, Hangzhou, China; bsun@zju.edu.cn.
authors.forename: Benyan
authors.initials: B
authors.lastname: Luo
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology, Ministry of Health of China, bsun@zju.edu.cn.|Key Laboratory of Neurobiology of Zhejiang Province, and.
authors.forename: Binggui
authors.initials: B
authors.lastname: Sun
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D018891:Dentate Gyrus / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D020813:Receptor, trkB / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C000604140:EFR3A protein, mouse; D008565:Membrane Proteins; D020813:Receptor, trkB
keywords: BDNF; Efr3; dentate gyrus; development; mouse