精神分裂症是多基因遗传的精神疾病，人群患病率约1%。越来越多证据显示精神分裂症患者存在神经发育障碍。中国汉族人群中进行的全基因组关联研究发现转录因子SOX11可能是精神分裂症易感基因，既往文献提示SOX11调控神经发育和神经可塑性。因此，我们认为SOX11基因可能通过调控下游神经发育通路影响精神分裂症的发病。本项目前期使用独立病例对照样本证实SOX11基因与精神分裂症关联，体外实验和小鼠子宫内穿孔结果显示SOX11参与神经发育多个阶段，包括神经干细胞增殖分化、神经突生长、神经元成熟和迁移。本项目将在三个方面进行研究：1)使用已构建的SOX11敲除小鼠模型观测其缺失后神经发育核心事件的改变；2)在已获得的表达谱芯片数据基础上，发现并验证神经发育过程中SOX11的下游基因；3)明确SOX11参与神经发育和神经可塑性的分子机制。本项目为揭示SOX11的致病机理和深入研究精神分裂症病因奠定基础。

Schizophrenia is a complex genetic neuropsychiatric disorder afflicting approximately 1% of the general population worldwide. Accumulating evidence revealed neurodevelopmental disturbances in patients with schizophrenia. Genome-wide association study (GWAS) applied in the Chinese Han population indicated that the transcriptional factor SOX11 gene may be a susceptibility gene for schizophrenia. Previous studies have showed that SOX11 is involved in early-stage neurodevelopment and neuroplasticity. Therefore, SOX11 may induce emergence of schizophrenia by regulating neurodevelopmental signaling. In our previous work, we verified the association of SOX11 and schizophrenia in an independent case-control sample-set, and the results of in vitro cell experiments and in utero electroporation showed that SOX11 was involved in multiple phases of neurodevelopment, including neural proliferation and differentiation, neuronal maturation, neurite growth and neuronal migration. In this project, we will focus on three research directions: 1) observe the core events in neurodevelopment in the constructed Sox11 deficient mouse model; 2) investigate the transcriptional profile of SOX11 in neurodevelopment based on cDNA array analysis; 3) explore the related molecular mechanism of SOX11 regulation in neurodevelopment and neuroplasticity. This project will provide important information for revealing the pathogenesis of schizophrenia susceptibility gene SOX11 and the further study of schizophrenia etiology.