Microglia are tissue-resident macrophages residing in the central nervous system (CNS) and play critical roles in removing cellular debris and infectious agents as well as regulating neurogenesis and neuronal activities. Yet, the molecular basis underlying the establishment of microglia pool and the maintenance of their homeostasis in the CNS remain largely undefined. Here we report the identification and characterization of a mutant zebrafish, which harbors a point mutation in the nucleotide-binding oligomerization domain (NOD) like receptor gene nlrc3-like, resulting in the loss of microglia in a temperature sensitive manner. Temperature shift assay reveals that the late onset of nlrc3-like deficiency leads to excessive microglia cell death. Further analysis shows that the excessive microglia death in nlrc3-like deficient mutants is attributed, at least in part, to aberrant activation of canonical inflammasome pathway. Our study indicates that proper regulation of inflammasome cascade is critical for the maintenance of microglia homeostasis.

小胶质细胞是驻留在中枢神经系统（CNS）中的驻留组织的巨噬细胞，在清除细胞碎片和感染因子以及调节神经发生和神经元活动中起关键作用。然而，在中枢神经系统中建立小胶质细胞池和维持其动态平衡的分子基础仍未明确。在这里，我们报告的突变斑马鱼的鉴定和表征，斑马鱼在核苷酸结合寡聚域（NOD）像受体基因nlrc3-like一样具有点突变，从而以温度敏感方式导致小胶质细胞的丢失。温度变化分析显示，nlrc3-like的起病较晚缺乏会导致小胶质细胞过度死亡。进一步的分析表明，nlrc3样缺陷型突变体中的小胶质细胞过度死亡至少部分归因于典型的炎性体途径的异常激活。我们的研究表明，炎性体级联反应的适当调节对于维持小胶质细胞稳态是至关重要的。