Netrin-G1 Regulates Microglial Accumulation along Axons and Supports the Survival of Layer V Neurons in the Postnatal Mouse Brain
Netrin-G1 Regulates Microglial Accumulation along Axons and Supports the Survival of Layer V Neurons in the Postnatal Mouse Brain
复制标题
DOI：
10.1016/j.celrep.2020.107580
复制
发表时间：
2020-04-28
期刊：
影响因子：
8.8
通讯作者：
Yamashita, Toshihide
中科院分区：
文献类型：
--
作者：
Fujita, Yuki;Nakanishi, Toru;Yamashita, Toshihide
小胶质细胞，中枢神经系统的常驻免疫细胞，在出生后早期期间沿着大脑下投射轴突积聚并支持神经元存活。小胶质细胞如何遵循轴突特异性分布模式来维持神经回路仍然是未知的。在这里，我们研究了小胶质细胞积累的机制，沿着脑下投射轴突，小胶质细胞积累在内囊是必要的。筛选参与小胶质细胞向第V层皮质神经元轴突积累的分子，鉴定出netrin-G1，其为具有糖基-磷脂酰肌醇锚的轴突引导分子netrin家族的成员。netrin-G1基因Ntng 1的缺失或敲低减少了小胶质细胞的积累，并导致皮质神经元的损失。与野生型小胶质细胞相比，Netrin-G1配体-Ngl 1敲除小鼠衍生的小胶质细胞显示出沿轴突的沿着积累减少。因此，小胶质细胞通过NGL 1-netrin-G1信号传导聚集在大脑下投射轴突周围，并支持神经元存活。我们的观察揭示了神经元和小胶质细胞之间的双向神经营养相互作用。
Microglia, the resident immune cells of the central nervous system, accumulate along subcerebral projection axons and support neuronal survival during the early postnatal period. It remains unknown how microglia follow an axon-specific distribution pattern to maintain neural circuits. Here, we investigated the mechanisms of microglial accumulation along subcerebral projection axons that were necessary for microglial accumulation in the internal capsule. Screening of molecules involved in this accumulation of microglia to axons of layer V cortical neurons identified netrin-G1, a member of the netrin family of axon guidance molecules with a glycosyl-phosphatidylinositol anchor. Deletion or knockdown of the netrin-G1 gene Ntng1 reduced microglial accumulation and caused loss of cortical neurons. Netrin-G1 ligand-Ngl1 knockout-mice-derived microglia showed reduced accumulation along the axons compared with wild-type microglia. Thus, microglia accumulate around the subcerebral projection axons via NGL1-netrin-G1 signaling and support neuronal survival. Our observations unveil bidirectional neurotrophic interactions between neurons and microglia.