EVA1A/TMEM166 Regulates Embryonic Neurogenesis by Autophagy

Li, Mengtao; Lu, Guang; Hu, Jia; Shen, Xue; Ju, Jiabao; Gao, Yuanxu; Qu, Liujing; Xia, Yan; Chen, Yingyu; Bai, Yun

doi:10.1016/j.stemcr.2016.01.011

Cited by 44 publications

(38 citation statements)

References 37 publications

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“…Further Gene Ontology analysis using the BINGO plugin also provided information about the molecular functions and cellular components associated with Eva1a, such as protein binding, and transcriptional factor binding. Furthermore, a previous study of the Eva1a −/− mouse showed that the Pik3ca-Akt-Mtor axis is involved in the EVA1A regulation network [4], which also confirmed our KEGG-based pathway enrichment analysis: the PI3K-Akt signaling pathway, Parkinson's disease, and Alzheimer's disease are all associated with the Eva1a regulation network.…”

Section: Discussionsupporting

confidence: 89%

“…5), we may infer that NNT plays an important role in the EVA1A network, mediating the progress of neuronal differentiation regulated by EVA1A. Because Eva1a is an autophagy-related gene, its loss may result in the disruption of neurogenesis during nervous system development [4], and may further reduce of neuronal differentiation in the mature brain. Therefore, Eva1a, NNT, and other related genes may be promising targets for drug discovery and further study of regulatory mechanisms.…”

Section: Discussionmentioning

confidence: 99%

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Quantitative proteomics reveals EVA1A‐related proteins involved in neuronal differentiation

et al. 2017

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EVA1A is an autophagy-related protein, which plays an important role in embryonic neurogenesis. In this study, we found that loss of EVA1A could decrease neural differentiation in the brain of adult Eva1a −/− mice. To determine the mechanism underlying this phenotype, we performed label-free quantitative proteomics and bioinformatics analysis using the brains of Eva1a −/− and wild-type mice. We identified 11 proteins that were up-regulated and 17 that were down-regulated in the brains of the knockout mice compared to the wild-type counterparts. Bioinformatics analysis indicated that biological processes, including ATP synthesis, oxidative phosphorylation, and the TCA cycle, are involved in the EVA1A regulatory network. In addition, gene set enrichment analysis showed that neurodegenerative diseases, such as Alzheimer's disease and Huntington's disease, were strongly associated with Eva1a knockout. Western blot experiments showed changes in the expression of nicotinamide nucleotide transhydrogenase, an important mitochondrial enzyme involved in the TCA cycle, in the brains of Eva1a knockout mice. Our study provides valuable information on the molecular functions and regulatory network of the Eva1a gene, as well as new perspectives on the relationship between autography-related proteins and neural differentiation.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Quantitative proteomics reveals EVA1A‐related proteins involved in neuronal differentiation

et al. 2017

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“…Our results also suggested that alterations in neurogenesis that are caused by Cln5 deficiency are not related to changes in hippocampal apoptosis. However, in addition to apoptosis, other mechanisms, such as autophagy, have been reported to modulate stem cell development and neurogenesis ( Wu et al, 2016 ; Li et al, 2016 ). Given that autophagy impairment is a central feature of the NCLs, it is possible that alterations in neurogenesis and autophagy are linked and should be further investigated.…”

Section: Discussionmentioning

confidence: 99%

Loss of CLN5 causes altered neurogenesis in a childhood neurodegenerative disorder

Savchenko

Singh

Konttinen

et al. 2017

Disease Models &Amp; Mechanisms

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Neural stem/progenitor cells (NPCs) generate new neurons in the brain throughout an individual's lifetime in an intricate process called neurogenesis. Neurogenic alterations are a common feature of several adult-onset neurodegenerative diseases. The neuronal ceroid lipofuscinoses (NCLs) are the most common group of inherited neurodegenerative diseases that mainly affect children. Pathological features of the NCLs include accumulation of lysosomal storage material, neuroinflammation and neuronal degeneration, yet the exact cause of this group of diseases remains poorly understood. The function of the CLN5 protein, causative of the CLN5 disease form of NCL, is unknown. In the present study, we sought to examine neurogenesis in the neurodegenerative disorder caused by loss of Cln5. Our findings demonstrate a newly identified crucial role for CLN5 in neurogenesis. We report for the first time that neurogenesis is increased in Cln5-deficient mice, which model the childhood neurodegenerative disorder caused by loss of Cln5. Our results demonstrate that, in Cln5 deficiency, proliferation of NPCs is increased, NPC migration is reduced and NPC differentiation towards the neuronal lineage is increased concomitantly with functional alterations in the NPCs. Moreover, the observed impairment in neurogenesis is correlated with increased expression of the pro-inflammatory cytokine IL-1β. A full understanding of the pathological mechanisms that lead to disease and the function of the NCL proteins are critical for designing effective therapeutic approaches for this devastating neurodegenerative disorder.

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“…One of the most significant reports looking at autophagy in neurogenesis indicated that in the absence of the autophagy gene FIP200, NSCs, NPCs, neuroblasts, and neurons in the hippocampus were dramatically reduced and this was accompanied by p53‐dependent apoptosis and cell cycle arrest . Other autophagy genes such as Beclin1, Ambra1, Atg5, Eva1a1 were shown to be highly expressed in the adult SVZ and were required for self‐renewal, survival, and differentiation of hippocampal neurons . Table summarizes the results of the studies implicating autophagy genes in neurogenesis.…”

Section: Autophagy In Neurogenesismentioning

confidence: 99%

Stress – (self) eating: Epigenetic regulation of autophagy in response to psychological stress

Puri

Subramanyam

2019

The FEBS Journal

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Autophagy is a constitutive and cytoprotective catabolic process. Aberrations in autophagy lead to a multitude of degenerative disorders, with neurodegeneration being one of the most widely studied autophagy‐related disorders. While the field has largely been focusing on the cytosolic constituents and processes of autophagy, recent studies are increasingly appreciating the role of chromatin modifications and epigenetic regulation in autophagy maintenance. Autophagy has been implicated in the regulation of neurogenesis, and disruption of neurogenesis in response to psychological stress is a proximal risk factor for development of neuropsychiatric disorders such as major depressive disorder (MDD). In this review, we will discuss the regulation of autophagy in normal neurogenesis as well as during chronic psychological stress, focusing on the epigenetic control of autophagy in these contexts, and also highlight the lacunae in our understanding of this process. The systematic study of these regulatory mechanisms will provide a novel therapeutic strategy, based on the use epigenetic regulators of autophagy to enhance neurogenesis and potentially alleviate stress‐related behavioral disorders.

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EVA1A/TMEM166 Regulates Embryonic Neurogenesis by Autophagy

Cited by 44 publications

References 37 publications

Quantitative proteomics reveals EVA1A‐related proteins involved in neuronal differentiation

Quantitative proteomics reveals EVA1A‐related proteins involved in neuronal differentiation

Loss of CLN5 causes altered neurogenesis in a childhood neurodegenerative disorder

Stress – (self) eating: Epigenetic regulation of autophagy in response to psychological stress

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