title: EVA1A/TMEM166 Regulates Embryonic Neurogenesis by Autophagy.
abstract: Self-renewal and differentiation of neural stem cells is essential for embryonic neurogenesis, which is associated with cell autophagy. However, the mechanism by which autophagy regulates neurogenesis remains undefined. Here, we show that Eva1a/Tmem166, an autophagy-related gene, regulates neural stem cell self-renewal and differentiation. Eva1a depletion impaired the generation of newborn neurons, both in vivo and in vitro. Conversely, overexpression of EVA1A enhanced newborn neuron generation and maturation. Moreover, Eva1a depletion activated the PIK3CA-AKT axis, leading to the activation of the mammalian target of rapamycin and the subsequent inhibition of autophagy. Furthermore, addition of methylpyruvate to the culture during neural stem cell differentiation rescued the defective embryonic neurogenesis induced by Eva1a depletion, suggesting that energy availability is a significant factor in embryonic neurogenesis. Collectively, these data demonstrated that EVA1A regulates embryonic neurogenesis by modulating autophagy. Our results have potential implications for understanding the pathogenesis of neurodevelopmental disorders caused by autophagy dysregulation.
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Mengtao
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Lu
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China; Peking University Center for Human Disease Genomics, Peking University, Beijing 100191, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Shen
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Jiabao
authors.initials: J
authors.lastname: Ju
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Yuanxu
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China; Peking University Center for Human Disease Genomics, Peking University, Beijing 100191, China.
authors.forename: Liujing
authors.initials: L
authors.lastname: Qu
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China; Peking University Center for Human Disease Genomics, Peking University, Beijing 100191, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China; Peking University Center for Human Disease Genomics, Peking University, Beijing 100191, China. Electronic address: yingyu_chen@bjmu.edu.cn.
authors.forename: Yingyu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China. Electronic address: baiyun@bjmu.edu.cn.
authors.forename: Yun
authors.initials: Y
authors.lastname: Bai
mesh_terms: D000818:Animals; D001343:Autophagy; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D055495:Neurogenesis; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C504470:Eva1 protein, mouse
keywords: Eva1a; autophagy; neural stem cells; neurodevelopmental disorder; neurogenesis