哺乳动物中枢神经系统神经元在脑发育早期呈现不对称性。所有神经突起中的一根会在发育过程中迅速生长形成轴突，并伴随轴突分支的形成，最终形成轴突-树突胞体的不对称形态。这一性质最终决定了神经回路的精确结构和正常功能。目前已知的影响神经元形态发育的因素包括微管微丝系统的稳定性、外部轴突诱导信号、轴突内部局部能量代谢、轴突膜结构形成以及轴突内部局部蛋白合成及降解代谢。细胞自噬作为重要的蛋白降解代谢途径，能清除神经元内部损伤衰老的细胞器，对于维持神经元正常功能至关重要。近期研究表明，自噬是轴突损伤再生和神经发育迟滞疾病模型的重要参与者。然而，自噬是否作为独立的信号调控神经元轴突发育尚缺乏详细报道。本项研究将利用神经元体外培养模型、胚胎电转体内模型、基因敲除小鼠模型探索自噬相关基因Atg12通过自噬通路调控轴突发育的分子机制。

Neurons of mammalian central nervous system show asymmetry in early brain development. One of all neurites grow rapidly during development, building up axons with the formation of axon branches, eventually forming a shape of asymmetric cell with both axon part and dendritic-cell part. This property ultimately determines the precise structure and normal function of the circuit. Factors known to affect neuron morphological development include the stability of the microtubule microfilament system, external axon induction signals, local energy metabolism within the axon, formation of axon membrane structures, and local protein synthesis and catabolic metabolism within the axon. Autophagy, as a critical protein degradation and metabolism pathway, clear the damaged and senescent organelles inside neurons, which is essential for maintaining the normal function of neurons. Recent studies showed that autophagy is a key signaling pathway for axonal regeneration events after injury, and also had been reported in neuro-developmental delay disease. However, it is still elusive on whether autophagy act as an independent signaling to regulate axonal development. In this study, we plan to explore molecular mechanism of autophagy-related 12 (Atg12) in regulating axonal development by utilizing in vitro neuronal culture model, in utero embryonic electroporation model, and CRISPR/Cas9 based gene knockout mouse model.