神经干细胞时龄调控（temporal regulation）是神经细胞多样性产生的基础，其是指在不同发育时间神经干细胞表现不同时龄特征（temporal identity），并产生不同子代细胞的过程。此过程在黑腹果蝇与哺乳类中比较保守。本课题组以黑腹果蝇神经干细胞为模型，通过筛选发现Pipsqueak基因家族dan/danr参与其中。前期数据表明dan/danr在神经干细胞表达，Dan/Danr的缺失导致神经干细胞终止的时龄特征前移。为了进一步探究其作用，课题组拟通过以下2点进行研究：1）全面分析dan/danr缺失对神经干细胞时龄特征的影响；2）通过TaDa-seq寻找Dan/Danr在神经干细胞中的特异结合位点，解析其调控分子机理。结合Pipsqueak基因家族成员特性，该课题的深入研究有望从染色体重塑的角度揭示神经干细胞时龄调控新网络，为细胞多样性产生与干细胞精确分化提供新的突破口。

The temporal regulation of neural stem cell is a fundamental strategy for cellular diversity. During development the neural stem cell shows distinct temporal idenetiy and generates diverse daughter cells, which is conserved between Drosophila melanogaster and mammalia. In order to further understand we performed MARCM screen and found the Drosophila Pipsqueak family genes member dan/danr were involoved in it. Our preliminary data showed that dan/danr is expressed in neural stem cells in Drosphila larval brain. Loss of Dan/Danr led to neural stem cell precocious differentiation and stemness defect after 72 hr ALH (after larval hatching). To fully characterize the role of dan/danr in the neural stem cell temporal regulation, these approaches are to use: cell biology, biochemistry, genetic mutant fly and TaDa-seq. Two specific aims are proposed to understand 1) How dan/danr contributes to temporal regulation by combining to the other temporal regulators, 2) what is the underlying mechanism by identification and characterization of novel dan/danr targets. This proposed study will address a novel transcriptional regulatory network and provide a new insight into the cellular diversity.