Microglia Modulate Wiring of the Embryonic Forebrain
Microglia Modulate Wiring of the Embryonic Forebrain
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DOI：
10.1016/j.celrep.2014.07.042
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发表时间：
2014-09-11
期刊：
影响因子：
8.8
通讯作者：
Garel, Sonia
中科院分区：
文献类型：
--
作者：
Squarzoni, Paola;Oller, Guillaume;Garel, Sonia
小胶质细胞（大脑的组织巨噬细胞）的功能障碍与几种神经精神疾病的病因有关。同时，小胶质细胞已被证明在围产期和出生后阶段调节神经发生和突触成熟。然而，小胶质细胞在胚胎发育中期侵入大脑，因此可能在产前发挥更早的作用。在这里，我们表明，胚胎小胶质细胞，显示短暂的不均匀分布，调节前脑电路的布线。使用多种小鼠模型，包括细胞耗竭方法和cx 3cr 1（-/-），CR 3（-/-），和DAP 12（-/-）突变体，我们发现，扰动小胶质细胞的活动会影响多巴胺能轴突的生长在前脑和新皮层中间神经元的亚群的层状定位。由于多巴胺神经支配和皮质网络的缺陷与神经精神疾病有关，我们的研究提供了关于小胶质细胞功能障碍如何影响前脑连接的见解，并揭示了免疫细胞在脑回路正常组装过程中的作用。
Dysfunction of microglia, the tissue macrophages of the brain, has been associated with the etiology of several neuropsychiatric disorders. Consistently, microglia have been shown to regulate neurogenesis and synaptic maturation at perinatal and postnatal stages. However, microglia invade the brain during mid-embryogenesis and thus could play an earlier prenatal role. Here, we show that embryonic microglia, which display a transiently uneven distribution, regulate the wiring of forebrain circuits. Using multiple mouse models, including cell-depletion approaches and cx3cr1(-/-), CR3(-/-), and DAP12(-/-) mutants, we find that perturbing microglial activity affects the outgrowth of dopaminergic axons in the forebrain and the laminar positioning of subsets of neocortical interneurons. Since defects in both dopamine innervation and cortical networks have been linked to neuropsychiatric diseases, our study provides insights into how microglial dysfunction can impact forebrain connectivity and reveals roles for immune cells during normal assembly of brain circuits.