多细胞生物的发育是一个复杂而高度程序化的过程，取决于细胞增值、分化、死亡、极性等多种行为的协同调控，而平面细胞极性(简称PCP)是发育过程中调控整体细胞极性、为组织器官形态发生提供方向性信息的关键机制。Wnt形态发生素被认为是建立PCP的关键信号，形成所谓的非经典Wnt/PCP信号通路，然而其信号传导机制未知、建立平面细胞极性的机理尚不清楚。本项目拟利用分子、生化、细胞和遗传学等手段，体外和体内实验相结合的方法，探索PCP核心蛋白Vangl2翻译后修饰参与Wnt/PCP信号传导的作用机制。我们的前期研究发现Wnt诱导的Vangl2磷酸化是平面细胞极性形成的关键步骤。在此基础上，我们将聚焦于Vangl2泛素化的调控机制及其与磷酸化的交互作用，揭示其调控Vangl2蛋白活性的重要功能。该研究有助于阐明Wnt/PCP信号通路的传导机制，对于揭示平面细胞极性建立的原理具有重要意义。

In the development of complex multicellular organisms, the formation of organs and tissues not only requires coordinated cell proliferation, differentiation and survival, but also cell polarity. Planar Cell Polarity (PCP) is a fundamental developmental process that conveys directional information for coordinated, uniformly polarized cellular behaviors in a field of cells. The uniform directionality of PCP is thought to be established by global cues such as Wnt morphogen gradients that induce a non-canonical Wnt/PCP signaling pathway. However, the underlying mechanism of signal transduction remains largely unknown. In this project, we propose to use a combination of genetic, biochemical and cell biological approaches to investigate the role of post-translational modification of Vangl2 in Wnt/PCP signaling pathway. Our previous studies found that Wnt-induced Vangl2 phosphorylation is critical for the establishment of PCP. In this project, we aim to elucidate the role of Vangl2 ubiquitination and its cross-talk with phosphorylation in transducing Wnt/PCP signaling. The successful completion of this research project will provide significant mechanistic insights into our understanding of PCP establishment and Wnt/PCP signal transduction.