神经轴突导向因子Slit及其受体Robo的起源和进化机理研究

Axon guidance molecule Slit and its receptor Robo play an important guiding role in the axon growth and the migration of neurons, muscle cells, leucocytes, vascular endothelial cells and cancer cells. However, their evolutionary ancestors and evolutionary mechanisms remain unclear. To identify the ancestors of Slit and Robo, we will clone homologues of Slit and Robo from hydra which is a ancestor animal of neural origin, and clarify their functions by using in situ hybridization,antibody staining, immunoprecipitation and transgenic fly technology. We will study the evolutionary mechanism of slit and Robo and how its functions were yielded by collecting and analyzing the homologous sequences of slit and Robo from hydra to human, and propose an evolutionary model of slit and Robo. This study has important significance for understanding the origin of the axon guidance molecules, and the formation mechanisms of the neural networks and brain. Meanwhile, it will provide a new theoretical basis on the treatment of neurological diseases and cancer clinical research.

神经轴突导向因子Slit及其受体Robo在轴突生长和神经细胞、肌肉细胞、白细胞、血管内皮细胞及癌细胞的迁移过程中起到重要的导向作用，然而其进化祖先和进化机制尚不清楚。本项目克隆神经起源的祖先动物水螅的Slit和Robo基因，利用原位杂交、抗体染色、免疫沉降及转基因果蝇等技术，对其功能进行解析，确定Slit和Robo的进化祖先；利用生物信息学技术，搜集水螅到人所有物种的Slit和Robo序列，进行典型物种的Slit和Robo序列的比对分析，探明Slit和Robo的功能是如何获得和进化的, 阐明其进化机理，利用进化学方法构建Slit和Robo的进化模型。本项目对于揭示神经轴突导向因子的起源、神经网络及大脑的形成机制具有重要的意义，还可以为防治神经系统疾病和癌症的临床研究提供新的理论依据。

神经轴突导向因子Slit及其受体Robo在轴突生长和神经细胞、肌肉细胞、白细胞、血管内皮细胞及癌细胞的迁移起到重要的导向作用，然而其进化祖先和进化机制尚不清楚。本项目克隆了神经起源的祖先动物水螅的Slit 和Robo基因，利用大肠杆菌表达了水螅Slit和Robo的重组蛋白，制作了水螅Slit和Robo的抗体，并进行了抗体染色。制作了水螅Slit 和Robo的转基因果蝇，为验证水螅Slit和Robo的功能奠定了基础。