Institute of Developmental Biology and Regenerative Medicine, Key Laboratory of Freshwater Fish Reproduction and Development, Ministry of Education, Southwest University, 400715, Chongqing, P.R. China.
Research Center of Stem Cells and Ageing, Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, 400714, Chongqing, P.R. China.
Nat Commun. 2022 Oct 17;13(1):6117. doi: 10.1038/s41467-022-33836-2.
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 bax zebrafish and Bax 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 Cx3cr1Rbpj 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.
小胶质细胞来源于原始髓样细胞，并在胚胎大脑中获得其早期特征。然而，大脑环境赋予小胶质细胞成熟特征的机制仍难以捉摸。在这里，我们证明 bax 斑马鱼和 Bax 小鼠胚胎表现出类似的早期小胶质细胞成熟缺陷。BAX 是一种典型的促凋亡因子，在神经元细胞中高度富集，并通过促凋亡和非凋亡机制调节小胶质细胞成熟。BAX 通过 CaMKII-CREB 轴钙依赖性地在活神经元中调节 dlb，同时确保凋亡神经元中迁入的前小胶质细胞中 Notch 的有效激活。Notch 信号在支持胚胎小胶质细胞成熟中是保守的。Cx3cr1Rbpj 胚胎小鼠中发生了受损的小胶质细胞发育；然而，当体外与 DLL3 孵育时，小胶质细胞获得了适当的特征。因此，我们的发现阐明了神经元环境在小胶质细胞发育中触发的 BAX-CaMKII-CREB Notch 网络，这可能为靶向神经元疾病治疗中的小胶质细胞提供创新思路。
Zotero 插件
