昼夜节律是哺乳动物行为与生理活动的基本特征。下丘脑视交叉上核（SCN）作为生物节律的起搏点，能响应外界光线变化，经细胞间的内部偶联、形成同步化的生物钟振荡，通过输出信号作用于下级神经元，从而在昼夜节律的调节中发挥中心作用。SCN可产生多种分泌性蛋白（如前动力蛋白Prok2），参与昼夜节律的信号输出；相关的调节机制尚不清楚。锌指蛋白ZBTB20是申请人自主发现的新分子，前期研究发现，该基因的神经系统特异性基因敲除小鼠自发活动的节律发生明显改变，表现为夜间活动的早期相受损和晚期相异常增强，与Prokr2缺陷小鼠类似；同时发现该小鼠SCN区的Prokr2表达下调。本课题拟在此基础上，通过行为学、组织学、细胞学与分子生物学等实验技术，深入研究神经系统中ZBTB20调节行为节律的细胞与分子学基础，明确靶基因Prokr2在ZBTB20调节行为节律中的地位，丰富人们对SCN节律调节网络的认识。

The mammals exhibit circadian rhythm in behavior and physiological processes. The hypothalamic suprachiasmatic nucleus (SCN) functions as a central circadian pacemaker, which is capable of adaptation to external light change by intercellular coupling and synchronizing core circadian oscillators. SCN neurons project to the target region with some relevant secretory proteins as the signals of circadian outputs, the underlying mechanisms remain poorly defined. The zinc finger protein ZBTB20, originally identified by the applicant, is implicated to have a potential role in the regulation of behavioral circadian rhythm according to our preliminary data. Specific deletion of ZBTB20 in nervous system led to a dramatic alteration of behavioral rhythm, with the evening locomotor activity impaired in the early phase but bursted in the late phase. The phenotypes are quite similar to that of Prokr2-deficent mice. Interestingly, Prokr2 expression was decreased in SCN from ZBTB20 mutant mice. With these preliminary data in hand, we proposed to investigate the cellular and molecular mechanisms by which ZBTB20 regulates circadian rhythm, and to validate whether Prokr2 is a critical target of ZBTB20 in circadian rhythm. Our research will broaden our knowledge about the regulatory network of circadian rhythm.