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  • br Introduction Neural stem cells NSCs are


    Introduction Neural stem cells (NSCs) are a class of multipotent cells responsible for generating all types of neural cells in the nervous system and for maintaining the stem cell population by self-renewal (Gage, 2000). The transition of proliferative and multipotent NSCs to fully differentiated neurons is called neurogenesis. Neurons are generated mainly from early embryonic development to early postnatal stages. After this phase, only a few neurogenic zones remain active in the adult AGI5198 (Gotz and Huttner, 2005; Ming and Song, 2011; Paridaen and Huttner, 2014). Embryonic neurogenesis is essential for the maintenance of NSCs, as well as for the generation of functional neural cell types and is therefore important for brain development and function. Autophagy is an evolutionarily conserved process in which cellular proteins and organelles are engulfed by autophagosomes and delivered to lysosomes for degradation. Autophagy is involved in a wide variety of physiological and pathological processes, such as cancer, immune and infectious diseases, and neurodegeneration (Jaeger and Wyss-Coray, 2009; Rosello et al., 2012). Among these diseases, the role of autophagy in neurodegeneration has been studied extensively. Deletion of autophagy-related genes, such as Atg5 and Atg7, caused dysregulation of autophagosome formation and consequent neurodegeneration (Komatsu et al., 2005, 2006; Kuma et al., 2004). In fact, many studies have suggested that modulators of autophagy may be used as potential therapeutic strategies to treat diseases caused by autophagy defects (Harris and Rubinsztein, 2012; Nassif and Hetz, 2011; Dalby et al., 2010). Although studies have suggested that autophagy has neuroprotective effects, the role of autophagy in regulating embryonic neurogenesis remains largely unknown. Previous studies have demonstrated that autophagy occurs in physiological conditions in the brain during the development of the nervous system and that it plays a significant role in cell differentiation (Schweichel and Merker, 1973; Zhao et al., 2010; Zeng and Zhou, 2008). Some autophagy-related genes that function in the inhibition of neurodegeneration are also essential for CNS development. Specifically, AMBRA1, an activating molecule in BECLIN 1-regulated autophagy, is essential for the development of the nervous system (Fimia et al., 2007; Yazdankhah et al., 2014; Vazquez et al., 2012). Another autophagy-related gene, Atg5, plays an important role in neurogenesis and gliogenesis. (Vazquez et al., 2012; Lv et al., 2014; Wang et al., 2014). These findings suggested a critical role of autophagy in the development of the nervous system. However, the precise mechanisms through which neurogenesis is regulated by autophagy is far from being well elucidated. Many molecular targets of this process need to be identified. EVA1A (Eva-1 homolog A), also known as TMEM166 (Transmembrane protein 166) or FAM176A (Family with sequence similarity 176), is a lysosome and ER-associated protein that can regulate cell autophagy and apoptosis (Wang et al., 2007). It is conserved in humans, chimpanzees, rats, mice, and dogs, indicating that it may have important functions in vertebrate animals. Previous studies revealed that EVA1A is expressed in a cell-type-specific and tissue-type-specific manner and is significantly downregulated in cancer tissues (Xu et al., 2013; Sun et al., 2012; Tao et al., 2015). In vivo and in vitro experiments demonstrated that EVA1A overexpression inhibits tumor cell proliferation by autophagy (Chang et al., 2013; Xie et al., 2014). These findings suggested a close correlation between EVA1A-induced autophagy and cancer suppression. Other studies have suggested that EVA1A-induced autophagy plays a significant role in cell death following focal cerebral ischemic injury (Li et al., 2012). Lu et al. (2015) demonstrated that EVA1A/TMEM166 is a key player in C/EBPα-mediated autophagy induction and protection against starvation. However, the role of EVA1A in neurogenesis has not been reported, and the mechanism by which EVA1A regulates autophagy remains to be determined.