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Brain milieu induces early microglial maturation through the BAX-Notch axis

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Listed:
  • Fangying Zhao

    (Southwest University)

  • Jiangyong He

    (Southwest University
    Chinese Academy of Sciences)

  • Jun Tang

    (Southwest University)

  • Nianfei Cui

    (Southwest University)

  • Yanyan Shi

    (Southwest University)

  • Zhifan Li

    (Southwest University)

  • Shengnan Liu

    (Southwest University)

  • Yazhou Wang

    (Fourth Military Medical University)

  • Ming Ma

    (Southwest University)

  • Congjian Zhao

    (Chongqing University of Posts and Telecommunications)

  • Lingfei Luo

    (Southwest University)

  • Li Li

    (Southwest University
    Chinese Academy of Sciences)

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.

Suggested Citation

  • Fangying Zhao & Jiangyong He & Jun Tang & Nianfei Cui & Yanyan Shi & Zhifan Li & Shengnan Liu & Yazhou Wang & Ming Ma & Congjian Zhao & Lingfei Luo & Li Li, 2022. "Brain milieu induces early microglial maturation through the BAX-Notch axis," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33836-2
    DOI: 10.1038/s41467-022-33836-2
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    3. Rong-wei Zhang & Xiao-quan Li & Koichi Kawakami & Jiu-lin Du, 2016. "Stereotyped initiation of retinal waves by bipolar cells via presynaptic NMDA autoreceptors," Nature Communications, Nature, vol. 7(1), pages 1-12, November.
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