Neural progenitor cells orchestrate microglia migration and positioning into the developing cortex
Neural progenitor cells orchestrate microglia migration and positioning into the developing cortex
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DOI：
10.1038/ncomms6611
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发表时间：
2014-11-01
影响因子：
16.6
通讯作者：
Muzio, Luca
中科院分区：
文献类型：
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作者：
Arno, Benedetta;Grassivaro, Francesca;Muzio, Luca
在早期发育的前脑中观察到小胶质细胞，并通过尚未阐明的机制参与神经发生的调节。在发育中的大脑皮层中，小胶质细胞聚集在心室/室下区（VZ/SVZ），该区域含有表达cxcl12的基底祖细胞（bp）。本研究表明，BP的消融以及Cxcl12的遗传缺失会影响小胶质细胞向SVZ的募集。Cxcl12异位表达或CxcR4的药理学阻断进一步支持了Cxcl12/CxcR4信号参与皮质发育过程中的小胶质细胞募集。此外，我们发现发育中的前脑细胞死亡触发小胶质细胞增殖，这是由巨噬细胞迁移抑制因子（MIF）的释放介导的。最后，我们发现在缺乏集落刺激因子-1受体（Csf-1R）的小鼠中，小胶质细胞的耗竭会减少bp进入大脑皮层。
Microglia are observed in the early developing forebrain and contribute to the regulation of neurogenesis through still unravelled mechanisms. In the developing cerebral cortex, microglia cluster in the ventricular/subventricular zone (VZ/SVZ), a region containing Cxcl12-expressing basal progenitors (BPs). Here we show that the ablation of BP as well as genetic loss of Cxcl12 affect microglia recruitment into the SVZ. Ectopic Cxcl12 expression or pharmacological blockage of CxcR4 further supports that Cxcl12/CxcR4 signalling is involved in microglial recruitment during cortical development. Furthermore, we found that cell death in the developing forebrain triggers microglial proliferation and that this is mediated by the release of macrophage migration inhibitory factor (MIF). Finally, we show that the depletion of microglia in mice lacking receptor for colony-stimulating factor-1 (Csf-1R) reduces BPs into the cerebral cortex.