神经干细胞的不对称分裂，是调控其自我更新和分化的一个重要途径，对于大脑的正常发育至关重要。然而相对于无脊椎动物，对于脊椎动物体内神经干细胞不对称分裂的调控机制尚缺乏系统的认识。本项目拟采用活体斑马鱼胚胎脑室电转、单细胞激光捕获、Single Cell RNA-seq 、镶嵌遗传学分析等技术，以发育中的斑马鱼神经干细胞为研究对象，在单细胞全转录组水平上，系统性地研究神经干细胞分裂所产生的成对子细胞中存在的差异表达基因，创建基因差异表达谱，鉴定2-3个显著性差异表达的关键基因或信号通路，揭示其对于神经干细胞不对称分裂的调控作用。研究结果将丰富对调控神经干细胞不对称分裂调控机制的认识。

Asymmetric division is an important way to regulate self-renewal and differentiation of neural stem cells, which is crucial to the brain development. However, compared to the invertebrates, much less is known about the regulation of asymmetric neural stem cell division in vertebrates. The present proposal will use brain ventricle-targeted electroporation, laser-based single cell microdissection, Single Cell RNA-seq, and genetic mosaic experiments to study the asymmetric division of neural stem cells at single-cell transcriptome resolution in the developing zebrafish brain. These studies will systemically explore the differentially expressed genes in paired daughter cells which are generated from asymmetric neural stem cell division, and identify 2 or 3 key genes or signaling pathway which are significantly differentially expressed in paired daughter cells. Further studies will be carried out to investigate how these molecular players regulate the asymmetric division of neural stem cells. The present study will advance the understanding of the regulation mechanisms of asymmetric neural stem cell division.