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。为寻找此信号通路的新调控因子，我们以果蝇Wnt信号调控的翅膀发育为模型，通过体内RNAi筛选发现了两个新基因tyd和sre。其中，tyd对Wnt信号传递起促进作用，sre对Wnt信号传递起抑制作用。利用果蝇RNAi株和减效等位基因株下调tyd和sre基因功能会干扰Wnt信号通路下游基因的表达,在翅膀和眼睛上特异性地影响Wnt信号所调控的器官发育。tyd能与Wnt信号通路的关键调控因子armadillo相互作用，而sre在Wnt信号通路中的位置处于frizzled和dishevelled之间。本申请项目拟在此工作基础上，结合基因敲除、基因敲低和基因过表达的方法，在果蝇体内、果蝇细胞系和人类癌症细胞系中深入研究tyd和sre及其同源蛋白调控Wnt信号通路的分子机理。

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. We used Drosophila Wnt signaling-regulated wing development as a model, performed an in vivo RNAi screen, and identified two genes tyd and sre as novel regulators. tyd has a positive role while sre has a negative role in Wnt signaling. tyd or sre RNAi or alleles interferes with expression of Wnt target genes, and affect Wnt regulated development in the eye or wing. We find that tyd interacts with armadillo, while sre functions between frizzled and disheveled. Based on these information, we plan to further study the mechanisms through which tyd and sre as well as their mammalian homologs regulate Wnt signaling in Drosophila and cancer cell lines via gene knock-out, knockdown and overexpression.