PUBLICATION

Mafba and Mafbb regulate microglial colonization of zebrafish brain via controlling chemotaxis receptor expression

Authors
Lou, L., Yu, T., Dai, Y., Zhao, S., Feng, S., Xu, J., Wen, Z.
ID
ZDB-PUB-220921-16
Date
2022
Source
Proceedings of the National Academy of Sciences of the United States of America   119: e2203273119 (Journal)
Registered Authors
Wen, Zilong
Keywords
Gpr34a, Mafb, colonization, lysoPS, microglia
Datasets
GEO:GSE213126
MeSH Terms
  • Animals
  • Brain/physiology
  • Chemotaxis
  • Mammals/metabolism
  • Microglia*/metabolism
  • Transcription Factors/metabolism
  • Zebrafish*/metabolism
PubMed
36122226 Full text @ Proc. Natl. Acad. Sci. USA
Abstract
Microglia are the central nervous system (CNS)-resident macrophages involved in neural inflammation, neurogenesis, and neural activity regulation. Previous studies have shown that naturally occurring neuronal apoptosis plays a critical role in regulating microglial colonization of the brain in zebrafish. However, the molecular signaling cascades underlying neuronal apoptosis-mediated microglial colonization and the regulation of these cascades remain undefined. Here, we show that basic leucine zipper (b-Zip) transcription factors, Mafba and Mafbb, two zebrafish orthologs of mammalian MAFB, are key regulators in neuronal apoptosis-mediated microglial colonization of the brain in zebrafish. We document that the loss of Mafba and Mafbb function perturbs microglial colonization of the brain. We further demonstrate that Mafba and Mafbb act cell-autonomously and cooperatively to orchestrate microglial colonization, at least in part, by regulating the expression of G protein-coupled receptor 34a (Gpr34a), which directs peripheral macrophage recruitment into the brain through sensing the lysophosphatidylserine (lysoPS) released by the apoptotic neurons. Our study reveals that Mafba and Mafbb regulate neuronal apoptosis-mediated microglial colonization of the brain in zebrafish via the lysoPS-Gpr34a pathway.
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