A literature review showed that Atg7 biological role was associated with the development and pathogenesis of nervous system, but very few reports focused on Atg7 role on neurogenesis at the region of spinal cord, so that we are committed to explore the subject. Atg7 expression in neural tube is incrementally increased during neurogenesis. Atg7 neural-specific knockout mice demonstrated the impaired motor function and imbalance of neuronal and glial cell differentiation during neurogenesis, which was similarly confirmed in primary neurosphere culture and reversely verified by Atg7 overexpression in unilateral neural tubes of gastrula chicken embryos. Furthermore, activating autophagy in neural stem cells (NSCs) of neurospheres did not rescue Atg7 deficiency-suppressed neuronal differentiation, but Atg7 overexpression on the basis of autophagy inhibition could reverse Atg7 deficiency-suppressed neuronal differentiation, which provides evidence for the existence of Atg7 role of autophagy-independent function. The underlying mechanism is that Atg7 deficiency directly caused the alteration of cell cycle length of NSCs, which is controlled by Atg7 through specifically binding Mdm2, thereby affecting neuronal differentiation during neurogenesis. Eventually, the effect of overexpressing Atg7-promoting neuronal differentiation was proved in spinal cord injury model as well. Taken together, this study revealed that Atg7 was involved in regulating neurogenesis by a non-autophagic signaling process, and this finding also shed light on the potential application in regenerative medicine.

文献综述表明Atg7的生物学作用与神经系统的发育和发病机制有关，但很少有报道关注Atg7在脊髓区域神经发生中的作用，因此我们致力于探索这一课题。 Atg7 在神经管中的表达在神经发生过程中逐渐增加。 Atg7 神经特异性敲除小鼠表现出神经发生过程中运动功能受损以及神经元和胶质细胞分化失衡，这在原代神经球培养中得到了类似的证实，并通过原肠胚鸡胚胎单侧神经管中 Atg7 过表达得到了反向验证。此外，激活神经球神经干细胞（NSC）中的自噬并不能挽救Atg7缺陷抑制的神经元分化，但在自噬抑制的基础上Atg7过表达可以逆转Atg7缺陷抑制的神经元分化，这为Atg7作用的存在提供了证据的自噬独立功能。其潜在机制是Atg7缺陷直接导致NSCs细胞周期长度的改变，Atg7通过特异性结合Mdm2来控制细胞周期长度，从而影响神经发生过程中的神经元分化。最终，过表达Atg7促进神经元分化的作用也在脊髓损伤模型中得到了证实。总而言之，这项研究揭示了 Atg7 通过非自噬信号过程参与调节神经发生，这一发现也揭示了其在再生医学中的潜在应用。