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Culturing Microglia from the Neonatal and Adult Central Nervous System
Published on: August 9, 2013
Brain milieu induces early microglial maturation through the BAX-Notch axis
Fangying Zhao1, Jiangyong He1,2, Jun Tang1
1Institute of Developmental Biology and Regenerative Medicine, Key Laboratory of Freshwater Fish Reproduction and Development, Ministry of Education, Southwest University, 400715, Chongqing, P.R. China.
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.
Insights
The study reveals that BAX in neurons regulates microglial maturation via a BAX-CaMKII-CREB-Notch pathway. This neuronal signaling is crucial for embryonic microglia development and offers therapeutic targets for neuronal disorders.
Area of Science:
- Neuroscience
- Developmental Biology
- Immunology
Background:
- Microglia originate from primitive myeloid cells and establish their identity in embryonic brains.
- The precise mechanisms by which the brain microenvironment influences microglial maturation are not fully understood.
Purpose of the Study:
- To elucidate the role of BAX in embryonic microglial maturation.
- To identify the signaling pathways involved in neuronal regulation of microglia development.
Main Methods:
- Utilized bax mutant zebrafish (baxcq55) and mouse (Baxtm1Sjk) embryos to assess microglial maturation.
- Investigated the BAX-CaMKII-CREB axis and Notch signaling in neuronal regulation of microglia.
- Examined microglial development in Cx3cr1Cre/+Rbpjfl/fl mice and in vitro cultures with DLL3.
Main Results:
- Defective early microglial maturation was observed in bax mutant embryos.
- BAX regulates microglial maturation through both pro-apoptotic and non-apoptotic neuronal mechanisms.
- A BAX-CaMKII-CREB-Notch signaling network, triggered by neuronal apoptosis and calcium signaling, was identified as critical for microglia maturation.
Conclusions:
- Neuronal BAX and its downstream signaling pathways are essential for embryonic microglia development.
- The findings highlight a novel neuronal-microglial communication axis crucial for brain development.
- This research offers potential therapeutic strategies for neuronal disorders by targeting microglial development.
