Pcdhαc2 is required for axonal tiling and assembly of serotonergic circuitries in mice.
Pcdhαc2 is required for axonal tiling and assembly of serotonergic circuitries in mice.
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小鼠轴突平铺和血清素能电路的组装需要 Pcdh alpha c2
DOI：
10.1126/science.aal3231
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发表时间：
2017-04-28
期刊：
影响因子：
--
通讯作者：
Maniatis T
中科院分区：
文献类型：
--
作者：
Chen WV;Nwakeze CL;Denny CA;O'Keeffe S;Rieger MA;Mountoufaris G;Kirner A;Dougherty JD;Hen R;Wu Q;Maniatis T
5-羟色胺能神经元将它们的轴突遍及整个大脑，并以空间填充的方式支配各种靶区域，导致它们的轴突末端的平铺布置，以允许5-羟色胺在靶神经元之间的最佳分配。在这里，我们表明，小鼠原钙粘蛋白α（Pcdhα）基因簇的条件性删除在多巴胺能神经元破坏局部轴突平铺和整体组装的多巴胺能回路，并导致抑郁样行为。基因解剖和表达谱分析表明，这一作用是由Pcdhαc2特异性介导的，Pcdhαc2是在多巴胺能神经元中表达的唯一Pcdhα亚型。我们的结论是，在相反的轴突自我回避，这需要单细胞身份介导的Pcdh多样性，一个单一的细胞类型的身份介导的共同C型Pcdh亚型是必需的轴突平铺和组装的pneumonergic电路。
Serotonergic neurons project their axons pervasively throughout the brain and innervate various target fields in a space-filling manner, leading to tiled arrangements of their axon terminals to allow optimal allocation of serotonin among target neurons. Here we show that conditional deletion of the mouse protocadherin α (Pcdhα) gene cluster in serotonergic neurons disrupts local axonal tiling and global assembly of serotonergic circuitries and results in depression-like behaviors. Genetic dissection and expression profiling revealed that this role is specifically mediated by Pcdhαc2, which is the only Pcdhα isoform expressed in serotonergic neurons. We conclude that, in contrast to neurite self-avoidance, which requires single-cell identity mediated by Pcdh diversity, a single cell-type identity mediated by the common C-type Pcdh isoform is required for axonal tiling and assembly of serotonergic circuitries.