Sema3b-Nrp1信号通路调控施旺细胞与无髓轴突相互作用形成Remak bundle的机制研究

施旺细胞分为成髓鞘施旺细胞(mSC)和不成髓鞘施旺细胞（NMSC）两类。mSC包绕大口径轴突生成髓鞘，NMSC包裹小口径轴突生成Remak bundle。相对于髓鞘形成的分子机制的快速研究进展，调控NMSC与无髓轴突相互作用形成Remak bundle的分子机制知之甚少。申请人前期通过单细胞测序技术发现Sema3b特异性表达于NMSC，同时Sema3b基因敲除小鼠Remak bundle的结构和功能均具有明显缺陷。因此，本项目将利用免疫荧光染色、原位杂交、扫描电镜三维重建、行为学测试以及施旺细胞-轴突体外培养等技术探究NMSC与无髓轴突通过Sema3b-Neuropilin1信号通路调控Remak bundle发育机制。研究结果将推动对Remak bundle形成机制的理解，并为Remak bundle功能缺陷相关疾病如神经病理性疼痛的治疗提供新的理论基础。

Myelinating Schwann cells (mSCs) and nonmyelinating Schwann cells (NMSCs) are two major phenotypes of Schwann cells that perform different functions. MSCs enwrap large caliber fibers in concentric layers of myelin sheath to form myelinated nerve fibers which allow rapid propagation of action potentials. NMSCs ensheath multiple small caliber fibers to form Remak bundles which are responsible for the transmission of pain or autonomic signals. Although the mechanisms of myelination are commonly known, the mechanism of interaction of NMSCs and unmyelinated axons forming Remak bundle have been understudied relative to myelination. Our preliminary work found that Sema3b is expressed specificly in non-myelinating Schwann cells (NMSC) according to the analysis of the transcripts of mSCs and NMSCs. And mice lacking Sema3b appear abnormal ultrastructure and the dysfunction of Remak bundle. In this project, immunostaining, in situ hybridyzation, 3d reconstruction from scanning electron microscopy, behavior test, Schwann cell-axon coculture, together with mouse genetics will be used continously to address the following question: How does the Sema3b-Neuropilin1 signaling pathway mediate the interaction of NMSCs and unmyelinated axons to form Remak bundle. Our finding will prompt us to understand the molecular mechanisms of the development of Remak bundle and provide a theoretical basis for the treatment of Remak bundle-deficient diseases such as neuropathic pain.