脊髓是重要的中枢神经系统组成部分，人的脊髓遭受损伤后功能很难恢复，其一个主要的原因是中枢神经细胞轴突缺乏再生功能。与哺乳动物不同，斑马鱼中枢神经能有效再生轴突并恢复功能，阐明其背后的机理将为治疗中枢神经损伤提供新的思路。包括巨噬细胞和中性粒细胞在内的髓样细胞对神经轴突再生起着复杂的作用,全面理解巨噬细胞和中性粒细胞在轴突再生过程中发挥的作用及其背后的细胞分子机理，可以为日后治疗脊髓损伤提供更好的策略与方法。我们发现irf8、mcoln1、dock2等巨噬细胞和中性粒细胞的斑马鱼突变体中中枢神经Mauthner细胞轴突再生能力受损，而在完全缺失髓样细胞的cebpα突变体中Mauthner细胞轴突再生能力进一步降低。与之相应，促轴突再生的col12a1a/b基因表达在cebpα突变体中表达降低。本项目计划研究斑马鱼巨噬细胞和中性粒细胞对Mauthner细胞轴突再生的作用及其背后的细胞分子机理。

The spinal cord is an important component of the central nervous system (CNS). Human hardly recovers after spinal cord injury. One of the main reasons is that the axons of CNS neurons are lack of regeneration ability. Unlike mammals, axons of CNS neurons in zebrafish regenerate efficiently. Unraveling the mechanism behind axon regeneration in zebrafish could provide new strategies for clinical treatment of spinal cord injury in human. Myeloid cells, mainly including macrophages and neutrophils, play complex roles in axon regeneration. Complete understanding of the functions and mechanisms of myeloid cells on axon regeneration could lead to avenues to promote axon regeneration. The Mauthner cell is one type of CNS neurons in zebrafish. We found that axon regeneration of Mauthner cells was impaired in zebrafish irf8, mcoln1 and dock2 mutants whose macrophages or neutrophils are defective. The axon regeneration defects became more severe in cebpα mutants, in which both macrophages and neutrophils are absent. Accordingly, the expression of col12a1a/b, which has been reported to promote axon regeneration, was significantly reduced in cebpα mutants. Here we propose to study the cellular and molecular mechanisms of macrophages and neutrophils on Mauthner cell regeneration in zebrafish.