EVA1A/TMEM166 Regulates Embryonic Neurogenesis by Autophagy.
EVA1A/TMEM166 Regulates Embryonic Neurogenesis by Autophagy.
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EVA1A/TMEM166 通过自噬调节胚胎神经发生
DOI：
10.1016/j.stemcr.2016.01.011
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发表时间：
2016-03-08
影响因子：
5.9
通讯作者：
Bai Y
中科院分区：
文献类型：
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作者：
Li M;Lu G;Hu J;Shen X;Ju J;Gao Y;Qu L;Xia Y;Chen Y;Bai Y
神经干细胞的自我更新和分化对于胚胎神经发生至关重要，而胚胎神经发生与细胞自噬有关。然而，自噬调节神经发生的机制仍然不明确。在这里，我们表明，Eva 1a/Tmem 166，自噬相关基因，调节神经干细胞自我更新和分化。Eva 1a耗竭损害了体内和体外新生神经元的产生。相反，EVA 1A的过表达增强了新生神经元的产生和成熟。此外，Eva 1a耗竭激活了PIK 3CA-AKT轴，导致雷帕霉素的哺乳动物靶标的激活和随后的自噬抑制。此外，在神经干细胞分化过程中，向培养物中加入丙酮酸甲酯挽救了Eva 1a耗竭诱导的有缺陷的胚胎神经发生，这表明能量可用性是胚胎神经发生中的一个重要因素。总的来说，这些数据表明EVA 1A通过调节自噬来调节胚胎神经发生。我们的研究结果对理解自噬失调引起的神经发育障碍的发病机制具有潜在的意义。EVA 1A缺失导致神经干细胞自我更新和分化缺陷EVA 1A通过PIK 3CA/AKT-mTOR途径调节自噬甲基丙酮酸、哌立福辛和雷帕霉素恢复Eva 1a −/−神经干细胞的神经发生Bai，Chen及其同事发现，Eva 1a缺失导致神经干细胞神经发生受损，沿着自噬减少，其与PIK 3CA/AKT-mTOR信号传导的激活负相关。EVA 1A过表达、丙酮酸甲酯、哌立福新或雷帕霉素治疗基本上挽救了Eva 1a −/− NSC神经发生缺陷，证明了EVA 1A在胚胎神经发生中的关键功能。
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. EVA1A is elevated during embryonic neurogenesis with enhanced autophagy activation EVA1A deletion results in defective self-renewal and differentiation of NSCs EVA1A modulates autophagy through the PIK3CA/AKT-mTOR pathway Methylpyruvate, perifosine, and rapamycine restore neurogenesis in Eva1a−/− NSCs Bai, Chen, and colleagues found that loss of Eva1a leads to impaired NSC neurogenesis, along with a decrease in autophagy, which was inversely associated with the activation of the PIK3CA/AKT-mTOR signaling. EVA1A overexpression, methylpyruvate, perifosine, or rapamycine treatment substantially rescued Eva1a−/− NSC neurogenesis deficiency, demonstrating the crucial function of EVA1A in embryonic neurogenesis.