Department of Clinical Laboratory Medicine, School of Laboratory Medicine and Life Science, Wenzhou Medical College, Wenzhou, Zhejiang, 325035, China.
Glia. 2013 May;61(5):710-23. doi: 10.1002/glia.22464. Epub 2013 Jan 30.
Schwann cells migrate along axons before initiating myelination during development and their migration facilitates peripheral nerve regeneration after injury. Axon guidance molecule Slit-2 is highly expressed during peripheral development and nerve regeneration; however, whether Slit-2 regulates the migration of Schwann cells remains a mystery. Here we show that Slit-2 receptor Robo-1 and Robo-2 were highly expressed in Schwann cells in vitro and in vivo. Using three distinct migration assays, we found that Slit-2 repelled the migration of cultured Schwann cells. Furthermore, frontal application of a Slit-2 gradient to migrating Schwann cells first caused the collapse of leading front, and then reversed soma translocation of Schwann cells. The repulsive effects of Slit-2 on Schwann cell migration depended on a Ca(2+) signaling release from internal stores. Interestingly, in response to Slit-2 stimulation, the collapse of leading front required the loss of F-actin and focal adhesion, whereas the subsequent reversal of soma translocation depended on RhoA-Rock-Myosin signaling pathways. Taken together, we demonstrate that Slit-2 repels the migration of cultured Schwann cells through RhoA-Myosin signaling pathways in a Ca(2+)-dependent manner.
施万细胞在发育过程中沿轴突迁移，然后开始髓鞘形成，其迁移有助于损伤后的周围神经再生。轴突导向分子 Slit-2 在周围发育和神经再生过程中高度表达；然而，Slit-2 是否调节施万细胞的迁移仍然是一个谜。在这里，我们表明 Slit-2 受体 Robo-1 和 Robo-2 在体外和体内的施万细胞中高度表达。使用三种不同的迁移测定法，我们发现 Slit-2 排斥培养的施万细胞的迁移。此外，Slit-2 梯度的额侧应用于迁移的施万细胞首先导致前导前沿的崩溃，然后逆转施万细胞的体转位。Slit-2 对施万细胞迁移的排斥作用取决于从内部储存中释放 Ca(2+)信号。有趣的是，响应 Slit-2 刺激，前导前沿的崩溃需要 F-肌动蛋白和焦点粘连的丧失，而随后的体转位的逆转取决于 RhoA-Rock-Myosin 信号通路。总之，我们证明 Slit-2 通过依赖 Ca(2+)的方式通过 RhoA-Myosin 信号通路排斥培养的施万细胞的迁移。
