FOXP1综合征是一种以精神发育迟缓，语言障碍及自闭症为特征的疾病。现有小鼠模型在揭示Foxp1功能时与人源模型还存在一定差异，且Foxp1作用于神经发育的分子机制尚不明确。Foxp1表达于纹状体且会上调Notch信号通路中的Ncor2和Snw1，而该通路参与和调控神经干细胞（NSCs）的发育与功能。因此我们推测转录因子Foxp1通过Notch信号通路调控NSCs的发育及功能。前期研究中我们在患者中发现一影响剪接的新突变（FOXP1:c.1652+5G>A）。因此，本项目拟以该患者淋巴细胞构建iPS细胞模型并诱导为NSCs，通过一系列细胞学及分子生物学技术研究Foxp1对NSCs功能及Notch通路信号的影响，明确Foxp1调控的目标基因并揭示转录调控机制。本项目的实施对阐明Foxp1在FOXP1综合征中导致智力障碍相关表型的分子机制有重要的意义，将为临床干预及诊治提供新思路。

Characterized by mental retardation with language impairment and with or without autistic features, FOXP1 syndrome is a kind of global developmental delay-related disorder. There are some differences in interpreting the function of Foxp1 between mice model and human model. And the molecular mechanism of Foxp1 on neurodevelopment remains unknown. Foxp1 expresses in the striatum. It has been reported that it would lead to Ncor2 and Snw1 up-regulation, while Ncor2- and Snw1-related Notch signal pathway plays an essential role in the development of neural stem cells (NSCs) and maintains its normal function. Therefore, we suspect that transcription factor Foxp1 would regulate the function of NSCs through the Notch signal pathway. We identified a novel de novo variant in the FOXP1 gene (c.1652+5 G>A) in an adult patient with FOXP1 syndrome. RNA analysis revealed that this variant would impact splicing of the FOXP1 and result in a truncated protein. In this project, we aim to generate iPSCs from patient’s cells, investigate the impacts of the mutated Foxp1 on iPSC induced NSCs, study the effect of Foxp1 on the Notch signal pathway, identify the target gene and reveal the molecular mechanism of transcriptional regulation by some cytological and molecular biological experiments. With the implementation of this project, the molecular mechanism of FOXP1 syndrome resulting in mental retardation could be demonstrated and new thoughts for clinical intervention and therapy of FOXP1 syndrome could be provided.