LGL1调控浦肯野细胞树突发育的分子机制研究

神经元树突正常形态的确立对神经环路的形成至关重要，其发育异常导致多种神经系统疾病。树突形态发生受多种内外信号调控，但目前对树突发育调控子，尤其是内源调控子挖掘不足，导致树突发育的分子机制仍不清楚。我们前期研究发现LGL1缺失造成小鼠浦肯野细胞树突发育异常，并伴有严重的运动能力失调。在此基础上，本研究拟以WT及Pcp2-LGL1-/-敲除小鼠为材料，进行以下研究：1）比较二者不同发育阶段树突的形态差异，并结合LGL1时空表达，明确LGL1调控树突发育的哪个阶段；2）比较二者树突发育中相关细胞组分的差异，明确LGL1如何在细胞水平上调控树突发育；3）利用RNAi及过表达介导的表型恢复实验，分析LGL1与已知树突发育关键基因的调控关系，并结合RNA-seq分析，挖掘LGL1上下游信号分子，最终解析LGL1调控树突发育分子机制，明确其在树突发育调控网络中的位置，为临床相关疾病的治疗提供理论支撑。

The normal dendrites morphology of neuron is vital for the formation of the neural circuits, and its abnormal development result in many diseases of the nervous system. Dendritic morphology is regulated by variety of internal and external signals, but currently, the regulation of dendritic development factor, especially the internal factors, make its molecular mechanism is still not clear enough. Our previous study found LGL1 deletion in mice caused dendrites dysplasia with severe movement disorder. On this basis, this study intends to use WT and Pcp2-LGL1-/- knockout mice as material, make the following research: 1) To compare the different development stages of dendritic morphology, and combining the spatial and temporal expression of LGL1, confirming which stage LGL1 regulation in dendritic development; 2) Compare the differences in the cell components of the dendritic development, and clarify how LGL1 regulates dendritic development at the cellular level; 3) Using RNAi and overexpression mediated phenotype recovery experiments, to analyze the relationship of LGL1 and the known gene related dendritic development, and combining the RNA-seq analysis, discovering the upstream and downstream signaling molecules of LGL1, eventually, making the molecular mechanism clear that LGL1 regulation of dendritic development, clarifying its position in the dendritic growth regulation network, providing theoretical support for clinical related disease.