投射神经元轴突生长异常与精神分裂症等精神性疾病休戚相关，相关的机制研究已成为神经生物领域一个热点。已有研究表明，孤儿核受体COUP-TFII基因在杏仁核与小脑的神经元分化中具有重要作用；然而，人们对COUP-TFII基因在投射神经元轴突发生过程中的功能知之甚少。我们预实验表明，腹侧前脑特异条件性COUP-TFII基因缺失，导致从海马投射到乳头体的穹窿完全消失；而COUP-TFII基因过表达，会导致小鼠胼胝体不能形成。这就提示COUP-TFII对于神经元轴突投射具有重要影响。利用这两种模型，本项目拟通过脑组织透明技术（CLARITY）详细地观察COUP-TFII缺失与过表达模型中轴突的具体走向；神经元培养的方法来研究COUP-TFII缺失与拯救对神经元轴突的影响；以及行为学的指标来评判相关的神经功能是否异常。本项目的开展，有利于进一步了解神经元轴突生长异常导致精神性疾病的分子机制。

Axon projection disorders often lead to some psychiatric diseases, and the inherent mechanisms have attracted increasing attention. Coup-tf II, an orphan nuclear receptor, has been reported to regulate the fate of neurons in amygdala and cerebellum during development. However, the specific impact that coup-tf II exerts on the progress of axon projection remains incompletely studied. Our preliminary results show that fornix is totally absent from mice with coup-tf II specifically deleted in the ventral telencephalon, while over expression of coup-tf II there leads to the failure of coupus callosum formation. To advance our research of the roles of coup-tf II in axon projection, we will first visualize the axon orientation in situ in detail with the technique of CLARITY, and then observe the axon morphology with coup-tf II gene both knocked down and rescued in cultured neurons. Finally the behavioral tests will be applied to evaluate neuronal functions involved. In conclusion, this research will facilitate to elaborate the mechanisms of psychiatric diseases caused by abnormal axon projection.