神经系统畸形对生长发育、智力认知造成严重影响。胼胝体发育不良是新生儿期可识别的结构畸形，多数原因不明，遗传因素可能是重要致病机制。本课题组前期在3个胼胝体发育不良患儿中均发现SYTL3基因异常，且证实Sytl3基因在小鼠胚胎期表达，提示该基因为胼胝体发育不良的候选致病基因。SYTL3基因编码突触样蛋白家族，尚未与疾病建立相关性，可能与轴突蛋白结合发挥作用。本课题拟1.采用免疫共沉淀和质谱筛选，研究SYTL3相互作用的候选蛋白；2.利用体外培养神经元系统，明确Sytl3对于神经元生长发育的作用，及Sytl3敲减/突变对于神经元发育的影响；3.采用胚胎电转技术，明确Sytl3基因敲减/突变对于小鼠神经系统结构的影响及对神经元、突触的影响；4.通过患儿体细胞诱导iPS分化神经元，明确突变体是否影响与NRXN1等蛋白的作用。以期阐明SYTL3基因在神经发育、胼胝体发育中的作用及其机制。

Neural malformation is a great harmful factor threatening human health. Agenesis of the corpus callosum is one of common and regernizble neural defects in newborns. The aetiology of agenesis of the corpus callosum is still unclear and genetic factors may be important in it. On the basis of our previous research works, we found 3 neonates with agenesis of the corpus callosum carrying SYTL3 gene deletion/mutation. Furthermore, we confirmed that Sytl3 gene expressed during embryological development in mouse. We intended to study the role of SYTL3 gene mutations on the development of corpus callosum. In this study: 1. Using co-immunoprecipitation and mass spectrometry, we will identify the candidate interactive proteins of SYTL3 in vitro; 2. Using mouse neurons cultured in vitro, the efects of wildtype and mutant SYTL3 gene on neuronal development, morphology and physiological characteristics will be investigated; 3. Using in utero electroporation, we will analyse the expression, protein location, and the effection on it’s related moleculars of SYTL3 mutation; 4. Get the fibroblasts from the patient with SYTL3 gene mutation, and induced the fibroblasts into pluripotent stem cells, and then further induced into neurons. Neuronal development and morphology, the role of SYTL3 gene in neuronal differentiation and maturation, and the effection on it’s related moleculars will be investigated. The purpose of this study is to clarify SYTL3 mutant effects on brain, corpus callosum development and mechanism involved.