PUBLICATION
Brain milieu induces early microglial maturation through the BAX-Notch axis
- Authors
- Zhao, F., He, J., Tang, J., Cui, N., Shi, Y., Li, Z., Liu, S., Wang, Y., Ma, M., Zhao, C., Luo, L., Li, L.
- ID
- ZDB-PUB-221019-1
- Date
- 2022
- Source
- Nature communications 13: 6117 (Journal)
- Registered Authors
- Li, Li, Luo, Lingfei, Zhao, CongJian
- Keywords
- none
- Datasets
- GEO:GSE183340
- MeSH Terms
-
- Calcium
- Zebrafish*
- Calcium-Calmodulin-Dependent Protein Kinase Type 2
- Brain
- bcl-2-Associated X Protein/genetics
- Mice
- Animals
- Microglia*
- PubMed
- 36253375 Full text @ Nat. Commun.
Citation
Zhao, F., He, J., Tang, J., Cui, N., Shi, Y., Li, Z., Liu, S., Wang, Y., Ma, M., Zhao, C., Luo, L., Li, L. (2022) Brain milieu induces early microglial maturation through the BAX-Notch axis. Nature communications. 13:6117.
Abstract
Microglia are derived from primitive myeloid cells and gain their early identity in the embryonic brains. However, the mechanism by which the brain milieu confers microglial maturation signature remains elusive. Here, we demonstrate that the baxcq55 zebrafish and Baxtm1Sjk mouse embryos exhibit similarly defective early microglial maturation. BAX, a typical pro-apoptotic factor, is highly enriched in neuronal cells and regulates microglial maturation through both pro-apoptotic and non-apoptotic mechanisms. BAX regulates dlb via the CaMKII-CREB axis calcium-dependently in living neurons while ensuring the efficient Notch activation in the immigrated pre-microglia by apoptotic neurons. Notch signaling is conserved in supporting embryonic microglia maturation. Compromised microglial development occurred in the Cx3cr1Cre/+Rbpjfl/fl embryonic mice; however, microglia acquire their appropriate signature when incubated with DLL3 in vitro. Thus, our findings elucidate a BAX-CaMKII-CREB-Notch network triggered by the neuronal milieu in microglial development, which may provide innovative insights for targeting microglia in neuronal disorder treatment.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping