Nlrc3-like is required for microglia maintenance in zebrafish

Tienan Wang^{a, e, #},
Bo Yan^{b, e, #
, ,},
Liang Lou^a,
Xi Lin^a,
Tao Yu^a,
Shuting Wu^a,
Qing Lu^c,
Wei Liu^d,
Zhibin Huang^d,
Mingjie Zhang^a,
Wenqing Zhang^{d
, ,},
Zilong Wen^{a
, ,}

a.
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
b.
Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, China
c.
Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, 200240, China
d.
Department of Developmental Biology, School of Basic Medical Sciences, South China University of Technology, Guangzhou, 510630, China
e.
Division of Life Science, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China

More Information

Corresponding author: E-mail address: bo.yan@shphc.org.cn (Bo Yan); E-mail address: mczhangwq@scut.edu.cn (Wenqing Zhang); E-mail address: zilong@ust.hk (Zilong Wen)

These authors contributed equally to this work.

摘要

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Abstract: 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.
- Zebrafish /
- Microglia /
- Inflammasome /
- NOD-like receptors
These authors contributed equally to this work.
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