EVA1A/TMEM166 Regulates Embryonic Neurogenesis by Autophagy

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 st...

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Main Authors: Mengtao Li, Guang Lu, Jia Hu, Xue Shen, Jiabao Ju, Yuanxu Gao, Liujing Qu, Yan Xia, Yingyu Chen, Yun Bai
Format: Article
Language:English
Published: Elsevier 2016-03-01
Series:Stem Cell Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S221367111600028X
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author Mengtao Li
Guang Lu
Jia Hu
Xue Shen
Jiabao Ju
Yuanxu Gao
Liujing Qu
Yan Xia
Yingyu Chen
Yun Bai
author_facet Mengtao Li
Guang Lu
Jia Hu
Xue Shen
Jiabao Ju
Yuanxu Gao
Liujing Qu
Yan Xia
Yingyu Chen
Yun Bai
author_sort Mengtao Li
collection DOAJ
description 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.
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spelling doaj.art-8d0bb4542d374bc68376e2faf00c3bd32022-12-22T03:56:23ZengElsevierStem Cell Reports2213-67112016-03-016339641010.1016/j.stemcr.2016.01.011EVA1A/TMEM166 Regulates Embryonic Neurogenesis by AutophagyMengtao Li0Guang Lu1Jia Hu2Xue Shen3Jiabao Ju4Yuanxu Gao5Liujing Qu6Yan Xia7Yingyu Chen8Yun Bai9Department of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, ChinaDepartment of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, ChinaDepartment of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, ChinaDepartment of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, ChinaDepartment of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, ChinaDepartment of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, ChinaDepartment of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, ChinaDepartment of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, ChinaDepartment of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, ChinaDepartment of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, ChinaSelf-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.http://www.sciencedirect.com/science/article/pii/S221367111600028Xneural stem cellsneurogenesisautophagyEva1aneurodevelopmental disorder
spellingShingle Mengtao Li
Guang Lu
Jia Hu
Xue Shen
Jiabao Ju
Yuanxu Gao
Liujing Qu
Yan Xia
Yingyu Chen
Yun Bai
EVA1A/TMEM166 Regulates Embryonic Neurogenesis by Autophagy
Stem Cell Reports
neural stem cells
neurogenesis
autophagy
Eva1a
neurodevelopmental disorder
title EVA1A/TMEM166 Regulates Embryonic Neurogenesis by Autophagy
title_full EVA1A/TMEM166 Regulates Embryonic Neurogenesis by Autophagy
title_fullStr EVA1A/TMEM166 Regulates Embryonic Neurogenesis by Autophagy
title_full_unstemmed EVA1A/TMEM166 Regulates Embryonic Neurogenesis by Autophagy
title_short EVA1A/TMEM166 Regulates Embryonic Neurogenesis by Autophagy
title_sort eva1a tmem166 regulates embryonic neurogenesis by autophagy
topic neural stem cells
neurogenesis
autophagy
Eva1a
neurodevelopmental disorder
url http://www.sciencedirect.com/science/article/pii/S221367111600028X
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