Department of Transfusion Medicine, Zhejiang Provincial People's Hospital of Hangzhou Medical College, Hangzhou, 310053, China; Institute of Neuroscience and Institute of Hypoxia Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
Institute of Neuroscience and Institute of Hypoxia Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
Mol Cell Neurosci. 2018 Oct;92:27-39. doi: 10.1016/j.mcn.2018.06.004. Epub 2018 Jun 27.
Olfactory ensheathing cells (OECs) migrate from olfactory epithelium towards olfactory bulb (OB), contributing to formation of the presumptive olfactory nerve layer during development. However, it remains unclear that molecular mechanism of regulation of OEC migration in OB. In the present study, we found that OECs highly expressed the receptors of semaphorin 3A (Sema3A) in vitro and in vivo, whereas Sema3A displayed a gradient expression pattern with higher in inner layer of OB and lower in outer layer of OB. Furthermore, the collapse assays, Boyden chamber migration assays and single-cell migration assays showed that Sema3A induced the collapse of leading front of OECs and inhibited OEC migration. Thirdly, the leading front of OECs exhibited adaptation in a protein synthesis-independent manner, and endocytosis-dependent manner during Sema3A-induced OEC migration. Finally, Sema3A-induced collapse of leading front was required the decrease of focal adhesion and a retrograde F-actin flow in a cofilin activation-dependent manner. Taken together, these results demonstrate that Sema3A as an inhibitive migratory factor for OEC migration through cofilin activation is involved in the formation of olfactory nerve layer.
嗅鞘细胞（OECs）从嗅上皮迁移到嗅球（OB），有助于在发育过程中形成推定的嗅神经层。然而，OEC 在 OB 中迁移的调节分子机制尚不清楚。在本研究中，我们发现 OECs 在体外和体内高度表达神经丝氨酸蛋白 3A（Sema3A）的受体，而 Sema3A 表现出梯度表达模式，在 OB 的内层中表达较高，在 OB 的外层中表达较低。此外，塌陷实验、Boyden 室迁移实验和单细胞迁移实验表明，Sema3A 诱导 OEC 前缘的塌陷并抑制 OEC 迁移。第三，OEC 的前缘表现出适应，在 Sema3A 诱导的 OEC 迁移中以蛋白质合成非依赖性和内吞作用依赖性的方式。最后，Sema3A 诱导的前缘塌陷需要依赖于肌动蛋白丝解聚蛋白 cofilin 的激活，从而减少粘着斑和逆行 F-actin 流。总之，这些结果表明，Sema3A 作为一种抑制性迁移因子，通过 cofilin 的激活参与嗅神经层的形成。
