Semaphorin-3F通过cGMP信号通路吸引小脑颗粒细胞的生长锥
发布时间：2018-10-20 18:33
【摘要】： 在大脑发育过程中，细胞外的各种因子引导着神经生长锥向着最终的目的地延伸，从而形成精密而复杂的神经网络。但是其中的分子机制仍然有许多还不清楚。Semaphorin家族是一个重要的神经导向因子家族，其中semaphorin-3F(Sema3F)是这个家族重要的成员，它在神经系统发育过程中发挥重要作用。近来又发现Sema3F基因突变和肿瘤的形成密切相关，这使得进一步研究这个导向分子的功能和信号转导机理变得更有意义。 为了研究该分子在小脑发育中的作用，我们运用了生长锥塌缩实验，生长锥转向分析，以及小脑组织块共培养方法，来观察Sema3F对培养的大鼠小脑颗粒神经元的轴突生长和细胞迁移过程中的作用。并进一步运用药理学实验来检测该分子作用的下游信号机制。 我们发现Sema3F的高亲和力受体neuropilin-2(Npn2)在小脑颗粒细胞中有高表达。在生长锥转向实验中，一个细胞外的Sema3F梯度能使培养的小脑颗粒神经元的轴突发生Npn2依赖的吸引性的转向。而且，在组织块共培养中，，分泌Sema3F的细胞团能使小脑颗粒细胞偏向它迁移。我们发现Sema3F的吸引性作用在cGMP信号通路被抑制时受阻断，在细胞内cGMP水平增加时被削弱。进而在生长锥塌缩实验中，我们发现Sema3F能减弱因抑制基础水平的cGMP而引起的颗粒细胞生长锥的塌缩反应。 总而言之，本研究发现Sema3F通过激活cGMP对小脑颗粒细胞的生长锥延伸和细胞迁移产生吸引性的导向作用。
[Abstract]:During the development of the brain, various extracellular factors lead the nerve growth cone to the final destination to form a sophisticated and complex neural network. However, many of the molecular mechanisms are still unclear. Semaphorin family is an important neuro-guiding factor family, in which semaphorin-3F (Sema3F) is an important member of this family, which plays an important role in the development of nervous system. Recently, it has been found that the mutation of Sema3F gene is closely related to tumor formation, which makes it more meaningful to further study the function and signal transduction mechanism of this guiding molecule. To study the role of the molecule in the development of the cerebellum, we used the growth cone collapse test, the growth cone shift analysis, and the co-culture of the cerebellar tissue mass. To observe the role of Sema3F in axonal growth and cell migration of cultured rat cerebellar granular neurons. Further pharmacological experiments were used to detect the downstream signaling mechanism of the molecule. We found that neuropilin-2 (Npn2), a high affinity receptor of Sema3F, is highly expressed in cerebellar granulosa cells. In the growth cone turning experiment, an extracellular Sema3F gradient can induce the Npn2 dependent attractiveness of the axons of cultured cerebellar granular neurons. Moreover, in tissue mass co-culture, the Sema3F secreting cell mass causes the cerebellar granulosa cells to migrate in favor of it. We found that the attraction of Sema3F was blocked when the cGMP signaling pathway was inhibited and weakened when the intracellular cGMP level increased. Furthermore, in the growth cone collapse experiment, we found that Sema3F can attenuate the collapse of granulosa cell growth cone caused by inhibition of cGMP at basic level. In conclusion, we found that Sema3F can induce the growth cone extension and cell migration of cerebellar granulosa cells by activating cGMP.
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2007
【分类号】：R33
本文编号：2284031
[Abstract]:During the development of the brain, various extracellular factors lead the nerve growth cone to the final destination to form a sophisticated and complex neural network. However, many of the molecular mechanisms are still unclear. Semaphorin family is an important neuro-guiding factor family, in which semaphorin-3F (Sema3F) is an important member of this family, which plays an important role in the development of nervous system. Recently, it has been found that the mutation of Sema3F gene is closely related to tumor formation, which makes it more meaningful to further study the function and signal transduction mechanism of this guiding molecule. To study the role of the molecule in the development of the cerebellum, we used the growth cone collapse test, the growth cone shift analysis, and the co-culture of the cerebellar tissue mass. To observe the role of Sema3F in axonal growth and cell migration of cultured rat cerebellar granular neurons. Further pharmacological experiments were used to detect the downstream signaling mechanism of the molecule. We found that neuropilin-2 (Npn2), a high affinity receptor of Sema3F, is highly expressed in cerebellar granulosa cells. In the growth cone turning experiment, an extracellular Sema3F gradient can induce the Npn2 dependent attractiveness of the axons of cultured cerebellar granular neurons. Moreover, in tissue mass co-culture, the Sema3F secreting cell mass causes the cerebellar granulosa cells to migrate in favor of it. We found that the attraction of Sema3F was blocked when the cGMP signaling pathway was inhibited and weakened when the intracellular cGMP level increased. Furthermore, in the growth cone collapse experiment, we found that Sema3F can attenuate the collapse of granulosa cell growth cone caused by inhibition of cGMP at basic level. In conclusion, we found that Sema3F can induce the growth cone extension and cell migration of cerebellar granulosa cells by activating cGMP.
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2007
【分类号】：R33
【共引文献】
相关期刊论文 前2条
1 黄倩;周雪;丁艳;彭谨;赵伟;章为;;针刺对备用背根节神经元NP-1表达的影响[J];四川大学学报(医学版);2006年03期
2 温华知;江洪;鲁志兵;胡笑容;吴兵;徐盛开;黄从新;;大鼠心肌梗死后梗死周边区Sema 3A的变化及其对心室颤动阈值的影响[J];中国心脏起搏与心电生理杂志;2009年05期
相关硕士学位论文 前3条
1 李佳多;Sema3A对小鼠骨髓来源的DC细胞表面分子B7-H3表达影响的实验研究[D];华中科技大学;2011年
2 丁艳;部分去背根后脊髓内Sema3A、NP-1及备用背根节内NP-1表达的变化[D];四川大学;2006年
3 黄倩;针刺对部分去背根猫DRG、脊髓背角中NP-1及Sema3A表达的影响[D];四川大学;2006年
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