精神分裂症发病原因复杂，临床症状多样。虽然已找到多个易感基因，但是对于许多单基因、多基因综合功能和病理机制还不清楚。我们利用相对低等的模式动物果蝇研究精神分裂症相关基因功能和调控机制。首先论述利用果蝇研究精神疾病基因功能的可行性，然后选择性研究一些重要易感同源基因如Vein/EGFR、dNR1及新发现的如 dys、trh等。通过Vein和dNR1/2的相关突变体等的初步实验表明抑制Vein和dNR1/2功能均能影响果蝇社交行为，比如雄性求偶行为异常，我们猜测该行为可能通过影响信息素信号传输的神经网络。果蝇Vein/EGFR信号调控胶质细胞-神经元相互作用，是腹神经束（VNC）等轴突发育的关键调节因子。我们的研究内容主要为Vein/EGFR对动物行为影响的细胞调控机制，包括找出一些关键的分子，及Vein与dNR1/2可能的相互关联作用。我们同时通过类似手段研究其他可能的易感基因的功能等。

Schizophrenia is a mental disorder with multiplex etiology and multiform clinical features. By human genetic studies we have identified a lot of candidate genes/sites for schizophrenia, and the next step it is to find out the function of single gene and multiple genes, and the underlying pathological mechanisms. We plan to investigate the function and the modulation mechanisms of some schizophrenia susceptibility genes on Drosophila Model, from molecular and cellular level to behavior effects. First, we will discuss the strategies to use Drosophila to study psychiatric disorders, like schizophrenia. Then we will focus on some important relevant genes, including Vein/EGFR, dNR1/2, trh, and dys. We have some transgenic lines, such as inhibiting the dNR1 or dNR2 by dsRNA, and over expression and mutants of Vein and EGFR et al. Our preliminary results show that reduced expression of dNR1 or dNR2 significantly leads to deficits in social behaviors, like altered male mating orientation. We propose that suppression of NMDA receptor expression may alter the pheromone neural circuits in the fly brain. Meanwhile, we notice that Vein/EGFR signaling maintains glia survival during axon guidance, especially for ventral nervous cord (VNC) longitudinal axon trajectory, which links the sensory and motor systems, including pheromone signaling. Vein and EGFR mutants also alter the male mating preference. So our research mainly includes the underlying cellular mechanisms of altered social behaviors induced by suppression of Vein/EGFR Signaling, and the possible functional interaction with NMDA receptor subunits. We also plan to find out the function of some new genes (such as trh and dys), which could be susceptible to schizophrenia, by using these well-defined approaches in our lab.