TCF/LEFs and Wnt signaling in the nucleus

T-cell factor/lymphoid enhancer factor (TCF/LEF) transcription factors are the major end point mediators ofWnt/Wingless signaling throughout metazoans. TCF/LEFs are multifunc-tional proteins that use their sequence-specific DNA-binding and context-dependent inter-actions to specify which genes will be regulated by Wnts. Much of the work to define their actions has focused on their ability to repress target gene expression when Wnt signals are absent and to recruit b-catenin to target genes for activation whenWnts are present. Recent advances have highlighted how these on/off actions are regulated by Wnt signals and sta-bilized b-catenin. In contrast to invertebrates, which typically contain one TCF/LEF protein that can both activate and repress Wnt targets, gene duplication and isoform complexity of the family in vertebrates have led to specialization, in which individual TCF/LEF isoforms have distinct activities. Wnt signals play important roles duringanimal development (Logan and Nusse 2004), as well as in adult tissues that are re-freshed and repaired by stem cells (Haegebarth and Clevers 2009). It is the essential function o