Transient microglial absence assists postmigratory cortical neurons in proper differentiation
Transient microglial absence assists postmigratory cortical neurons in proper differentiation
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DOI：
10.1038/s41467-020-15409-3
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发表时间：
2020-04-02
影响因子：
16.6
通讯作者：
Miyata, Takaki
中科院分区：
文献类型：
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作者：
Hattori, Yuki;Naito, Yu;Miyata, Takaki
在发育中的皮层，迁移后神经元聚集在皮层板（CP），以正确区分巩固亚型身份。小胶质细胞，尽管他们广泛的调查活动，暂时从midembryonic CP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，小胶质细胞双向迁移通过吸引CXCL12释放的脑膜和脑室下区，从而退出midembryonic 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postmigration和体外生长的CP神经元表现出异常分化，与功能性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，这种作用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，“sanctualization”从小胶质细胞在midembryonic CP是必要的神经元适当微调的表达所需的分子进行适当的分化，从而确保功能性皮层电路的建立。中胚期小胶质细胞暂时从皮质板消失。这项研究表明，小胶质细胞暂时缺席皮层板所需的迁移后神经元，以适当微调其适当分化所需的分子的表达。
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. Microglia temporarily disappear from the cortical plate in the midembryonic stage. This study demonstrated that microglial transient absence from the cortical plate is required for postmigratory neurons to appropriately fine-tune the expression of molecules needed for their proper differentiation.