Shtn1对视网膜和视神经发育及再生的调控作用及其机制研究

视网膜和视神经是视觉通路的起点，它们的异常将严重影响视力，以致失明。Shtn1是脊椎动物独有的特异表达于神经组织的独特基因。在体外培养的神经元中的研究表明Shtn1通过与细胞骨架蛋白相互作用决定神经元的极性和轴突生长。但是Shtn1体内调控神经元轴突，特别是视神经，发育和生长的研究尚缺乏。我们的预实验研究结果显示，shtn1功能缺失，将导致斑马鱼出现小眼畸形和视神经发育不良。在本项目中，我们将主要以基因敲除和morpholino敲降斑马鱼为模型，结合体外制备培养的小鼠和人的视网膜节细胞，采用发育生物学，分子生物学，生物化学，高通量测序，质谱分析等多种生物学手段，研究Shtn1调控视网膜发育，视网膜节细胞轴突生长与再生的细胞和分子机理。

The retina and the optic nerve are the starting point of the visual pathway, defects of which will severely affect vision and are the major cause for blindness. Shtn1 is a nervous system specific gene that is unique to vertebrates. Studies in cultured hippocampal neurons showed that Shtn1 promotes asymmetry establishment in neurons, and thus determines axon formation and promotes axon growth. However, it is not clear whether and how Shtn1 regulates axons, especially retinal ganglion cell axons, formation and growth in vivo. Our preliminary study showed that knocking down shtn1 by morpholino embryo injection caused microphthalmia and optic nerve growth and projection defects in zebrafish. In this proposed study, we plan to use shtn1-knockout zebrafish and morpholino-knock down zebrafish as major model system, together with cultured mouse and human retinal ganglion cells, to characterize the roles and mechanism of Shtn1 in retina development and optic nerve development and regeneration.