Department of Anatomy and Cell Biology, Graduate School of Medicine, Nagoya University, Nagoya, Japan.
Japan Society for the Promotion of Science, Tokyo, Japan.
Nat Commun. 2020 Apr 2;11(1):1631. doi: 10.1038/s41467-020-15409-3.
In the developing cortex, postmigratory neurons accumulate in the cortical plate (CP) to properly differentiate consolidating subtype identities. Microglia, despite their extensive surveying activity, temporarily disappear from the midembryonic CP. However, the mechanism and significance of this absence are unknown. Here, we show that microglia bidirectionally migrate via attraction by CXCL12 released from the meninges and subventricular zone and thereby exit the midembryonic CP. Upon nonphysiological excessive exposure to microglia in vivo or in vitro, young postmigratory and in vitro-grown CP neurons showed abnormal differentiation with disturbed expression of the subtype-associated transcription factors and genes implicated in functional neuronal maturation. Notably, this effect is primarily attributed to interleukin 6 and type I interferon secreted by microglia. These results suggest that "sanctuarization" from microglia in the midembryonic CP is required for neurons to appropriately fine-tune the expression of molecules needed for proper differentiation, thus securing the establishment of functional cortical circuit.
在发育中的皮质中，迁移后的神经元在皮质板（CP）中积累，以正确分化巩固的亚型身份。尽管小胶质细胞具有广泛的探测活动，但它们暂时从胚胎中期 CP 中消失。然而，这种缺失的机制和意义尚不清楚。在这里，我们表明小胶质细胞通过趋化因子 CXCL12 的吸引力双向迁移，该趋化因子由脑膜和室下区释放，并由此离开胚胎中期 CP。在体内或体外非生理性过度暴露于小胶质细胞后，年轻的迁移后和体外培养的 CP 神经元表现出异常分化，与功能神经元成熟相关的亚型相关转录因子和基因的表达受到干扰。值得注意的是，这种效应主要归因于小胶质细胞分泌的白细胞介素 6 和 I 型干扰素。这些结果表明，胚胎中期 CP 中的小胶质细胞“隔离”对于神经元适当调整正确分化所需的分子表达是必要的，从而确保功能性皮质回路的建立。
