进化中高度保守的Wnt信号通路在器官发育、能量代谢和干细胞维持等过程中发挥重要作用，并与多种疾病的发生有密切联系。Wnt信号的传递途径除了经典的beta-Catenin通路外，还包括钙离子通路、PCP通路、Ror通路，以及人们了解最少的Ryk通路。非经典的Wnt受体Dnt是果蝇Ryk家族成员。申请人在前期工作中构建了dnt突变体和过表达株，并结合RNA干扰株，发现dnt的缺失或表达水平的改变能影响果蝇的个体大小、抗氧化应激能力、运动能力和寿命。虽然Wnt信号通路的生物学功能极为广泛，但上述作用还从未见报道。进一步工作表明Dnt与JNK有遗传学相互作用。本项目拟探索Wnt信号通过Dnt介导的传递途径，发现相关的调控因子、信号转导机制和关键的靶基因，阐明Wnt-Dnt-JNK介导的信号通路在果蝇生长与衰老过程中的生理功能。

Evolutionally conserved Wnt signaling pathway plays important roles in organ development, energy homeostasis and stem cell maintenance, and is implicated in the onset of many diseases. In addition to canonical beta-Catenin pathway, Wnt signal can be transduced via the Calcium pathway, the PCP pathway, the Ror pathway and less studied Ryk pathway. Noncanonical Wnt receptor Dnt belongs to the Drosophila Ryk family. Via dnt mutant, RNAi lines and overexpression lines, we found that loss of dnt or altering its expressing levels could affect Drosophila body size, oxidative stress resistance, climbing activity and longevity, which was never reported as functions of Wnt signaling. Further study showed that Dnt genetically interacted with JNK. This project aims to explore Dnt mediated Wnt signaling, discover key regulators, target genes and underlying mechanisms, and understand biological functions of the Wnt-Dnt-JNK pathway during Drosophila growth and aging.