Nlrc3-like is required for microglia maintenance in zebrafish

作     者：Tienan Wang Bo Yan Liang Lou Xi Lin Tao Yu Shuting Wu Qing Lu Wei Liu Zhibin Huang Mingjie Zhang Wenqing Zhang Zilong Wen 

作者机构：Division of Life Science and State Key Laboratory of Molecular Neuroscience Center of Systems Biology and Human Health The Hong Kong University of Science and Technology Clearwater Bay Kowloon Hong Kong China Shanghai Public Health Clinical Center Fudan University Shanghai 201508 China Bio-X Institutes Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders Ministry of Education Shanghai Jiao Tong University Shanghai 200240 China Department of Developmental Biology School of Basic Medical Sciences South China University of Technology Guangzhou 510630 China Division of Life Science Hong Kong University of Science and Technology Clear Water Bay Kowloon Hong Kong China 

出 版 物：《Journal of Genetics and Genomics》 (遗传学报（英文版）)

年 卷 期：2019年第46卷第6期

页      面：291-299页

核心收录：

学科分类：0710[理学-生物学] 1001[医学-基础医学(可授医学、理学学位)] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China (81801977, 31761163008) Shanghai Sailing Program (18YF1420400) the Outstanding Youth Training Program of Shanghai Municipal Health Commission (2018YQ54) the Research Grants Council of the HKSAR (16102414 HKUST5/CRF/ 12R AoE/M-09/12, and T13-607/12R) the Innovation and Technology Commission of the HKSAR (ITCPD/17-9) 

主　　题：Zebrafish Microglia Inflammasome NOD-like receptors 

摘      要：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.