Context-dependent bidirectional modulation of Wnt/β-catenin signaling

Wnt/β-catenin signaling is an evolutionarily conserved signaling system that controls cell proliferation, fate specification, differentiation, survival, and death. This signaling system is used repeatedly during embryogenesis and organogenesis and has diverse context-dependent functions in different aspects. Extensive investigations during the past three decades have clarified the core components that mediate Wnt/β-catenin signaling in all cells. However, to understand the mechanisms by which Wnt/β-catenin signaling exerts context-specific roles, it is also important to identify the context-dependent modulators of Wnt/β-catenin signaling. Recently, we and others discovered that Nemo-like kinase (NLK) and dimerization partner 1 (DP1) can regulate Wnt/β-catenin signaling positively and negatively in a cellular context-dependent manner and demonstrated that they play essential roles in embryonic development by fine-tuning cellular response to Wnt/β-catenin signaling. In this chapter, I summarize the function of the context-dependent bidirectional Wnt/β-catenin signaling modulators, with particular focus on NLK and DP1, and discuss the significance of the bidirectional modulation in embryonic development.