Wnt proteins are secreted signaling molecules that regulate cell-to-cell interactions during embryogenesis in many different tissues and species. Wnt signaling is required for normal thymocyte development, most dramatically at the pro-T-cell stage, although recent reports also indicate a role for Wnt proteins in later stages of thymocyte differentiation. The Wnt cascade induces the interaction of the normally cytoplasmic cofactor beta-catenin with the nuclear Tcf and Lef transcription factors. Active Wnt signaling is an absolute requirement for T-cell development, as demonstrated by the complete block in thymocyte development observed in the absence of Tcf1 and Lef1, or in the presence of extracellular Wnt inhibitors.