Casano Alessandra Maria, Albert Marvin, Peri Francesca
Developmental Biology Unit, European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany.
Developmental Biology Unit, European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany.
Cell Rep. 2016 Jul 26;16(4):897-906. doi: 10.1016/j.celrep.2016.06.033. Epub 2016 Jul 14.
In the brain, neurons that fail to assemble into functional circuits are eliminated. Their clearance depends on microglia, immune cells that colonize the CNS during embryogenesis. Despite the importance of these cells in development and disease, the mechanisms that target and position microglia within the brain are unclear. Here we show that, in zebrafish, attraction of microglia into the brain exploits differences in developmental neuronal apoptosis and that these provide a mechanism for microglial distribution. Reducing neuronal cell death results in fewer microglia, whereas increased apoptosis enhances brain colonization, resulting in more microglia at later stages. Interestingly, attraction into the brain depends on nucleotide signaling, the same signaling system used to guide microglia toward brain injuries. Finally, this work uncovers a cell-non-autonomous role for developmental apoptosis. Classically considered a wasteful process, programmed cell death is exploited here to configure the immune-neuronal interface of the brain.
在大脑中，未能组装成功能回路的神经元会被清除。它们的清除依赖于小胶质细胞，小胶质细胞是在胚胎发育过程中定殖于中枢神经系统的免疫细胞。尽管这些细胞在发育和疾病中很重要，但小胶质细胞在大脑中的靶向定位机制尚不清楚。在这里，我们表明，在斑马鱼中，小胶质细胞向大脑的吸引利用了发育性神经元凋亡的差异，并且这些差异为小胶质细胞的分布提供了一种机制。减少神经元细胞死亡会导致小胶质细胞数量减少，而凋亡增加会增强大脑定殖，导致后期小胶质细胞数量增多。有趣的是，小胶质细胞向大脑的吸引依赖于核苷酸信号传导，这与引导小胶质细胞趋向脑损伤的信号系统相同。最后，这项研究揭示了发育性凋亡的非细胞自主作用。程序性细胞死亡传统上被认为是一个浪费的过程，而在这里它被用来构建大脑的免疫 - 神经元界面。
