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.

在发育中的皮层中，迁移后的神经元积聚在皮层板（CP）中，以正确地区分巩固的亚型身份。小胶质细胞尽管有广泛的调查活动，但暂时从中胚层CP消失。但是，这种缺失的机理和意义尚不清楚。在这里，我们显示小胶质细胞通过吸引从脑膜和脑室下带释放的CXCL12双向迁移，从而退出中胚层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生长的CP神经元显示异常分化，亚型相关转录因子和功能神经元成熟相关基因的表达受到干扰。值得注意的是 这种作用主要归因于小胶质细胞分泌的白介素6和I型干扰素。这些结果表明，神经元需要对微胶质细胞中胚层CP中的“胶质细胞进行消毒”，以适当地微调适当分化所需分子的表达，从而确保功能性皮层回路的建立。