PUBLICATION

Tripartite-motif family protein 35-28 regulates microglia development by preventing necrotic death of microglial precursors in zebrafish

Authors
Yu, T., Kuang, H., Chen, J., Lin, X., Wu, Y., Chen, K., Zhang, M., Zhang, W., Wen, Z.
ID
ZDB-PUB-200514-1
Date
2020
Source
The Journal of biological chemistry   295(26): 8846-8856 (Journal)
Registered Authors
Chen, Jiahao, Wen, Zilong, Zhang, Wenqing
Keywords
Trim, cell death, development, macrophage, microglia, zebrafish
MeSH Terms
  • Animals
  • Microglia/cytology*
  • Microglia/physiology
  • Mutation, Missense
  • Necroptosis
  • Neural Stem Cells/cytology*
  • Neural Stem Cells/metabolism
  • Neurogenesis
  • Zebrafish/embryology*
  • Zebrafish/genetics
PubMed
32398256 Full text @ J. Biol. Chem.
Abstract
Microglia are tissue-resident macrophages in the central nervous system (CNS) that play essential roles in the regulation of CNS development and homeostasis. Yet, the genetic networks governing microglia development remain incompletely defined. Here, we report the identification and characterization of a microglia-defective zebrafish mutant wulonghkz12 (wulhkz12 ) isolated from an ethylnitrosourea (ENU)-based genetic screen. We show that wulhkz12 mutants harbors a missense point mutation in the gene region encoding the PRY/SPRY domain of the tripartite-motif family protein 35-28 (trim35-8) gene. Time-lapse imaging revealed that the loss of Trim35-28 function causes lytic necrosis of microglial precursors/peripheral macrophages, as indicated by cytoplasmic swelling and membrane rupture of these precursors and accompanied by neutrophil infiltration and systemic inflammation. Intriguingly, the lytic necrosis of microglial precursors in trim35-28-deficient mutants appeared to depend neither on the canonical pyroptotic nor on necroptotic pathways, as inhibition of the key component in each pathway could not rescue the microglia phenotype in trim35-28-deficient mutants. Finally, results from tissue-specific rescue experiments suggested that Trim35-28 acts cell-autonomously in the survival of microglial precursors. Taken together, the findings of our study reveal Trim35-28 as a regulatory protein essential for microglia development.
Genes / Markers
Figures
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Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes