动物模型是研究神经系统发育及疾病的重要工具，申请人长期致力于以线虫、斑马鱼为模型，针对神经发育及功能的核心问题的研究，在Cell，Nature，Neuron等顶级期刊发表了一系列重要成果。曾在国际首次发现正/负链RNA对基因表达的影响，为之后RNAi的发现和应用奠定了基础。气候揭示的foggy基因通过影响转录延伸来调节神经系统成熟及多巴胺能神经元凋亡，及par-1和notch通路在神经干细胞增殖和分化中的作用，为神经发育和疾病的研究开辟了新的方向。项目合作者为国内儿童癫痫性脑病诊断及治疗领域的权威，在儿童癫痫等神经系统疾病的临床诊疗和基础研究方面积累了丰富的资源和经验。合作双方已获得了一系列成果，其构建的mbd5敲除斑马鱼表现出与病人相似的脑发育及行为的异常，为将来针对mbd5及表观遗传异常导致的神经系统发育性疾病的基础研究及药物和治疗手段的开发提供了动物模型。

Model organisms have shown great potential in the pathogenesis study and drug development of complex neurological disorders. Applicant has wealthy experience in utilizing Zebrafish and C.elegans to investigate key questions in neural development and disease, and published a serial of important discovery in top journals such as Cell, Nature, and Neuron etc. As the first author, applicant reported the interference of (+/-)RNA in gene expression, which leads to the identification of RNAi, one of the most important discoveries in last two decades. Applicant also reported for the first time the indispensable role of foggy in regulating neuronal growth and maturation, as long as the role of Par-1 and Notch signaling in neural stem cell proliferation and differentiation. All this work has opened a new field of neuroscience. The collaborator of this project is a well-known neural pediatrics expert in one of the best children’s hospital, who has accumulated wealthy biological samples of patients and fruitful achievements in basic research. She is also one of the first investigators in studying the role of MBD5 in neural development disorders. During one year collaboration, we have created the first zebrafish mbd5 knockout model, which exhibited morphological disorders as patients in brain development, function, and behavior. In this projects, we will utilize this transgenic animal model to systematically investigate the role mbd5 in neural development particularly in the brain, to reveal the pathogenesis of mbd5 and epigenetic related neurological disorders.