Wnt signaling is required for thymocyte development and activates Tcf-1 mediated transcription

T cell factor/lymphocyte enhancer factor (Tcf/Lef) transcription factors co mplex with the transcriptional co-activator beta -catenin to transduce Wnt signals in a variety of developmental systems. The prototypic family member Tcf-1 is highly expressed in T lineage cells. Tcf1(-/-) mice are defective in cell cycling of early thymocyte stages. Here, we show that the interact ion of beta -catenin with Tcf-1 is required for full thymocyte development. This interaction may be established by signals mediated by Wnt1 and Wnt4, leading to increased Tcf-dependent transcriptional activity in thymocytes, as demonstrated in Tcf-LacZ reporter mice. Transduction of fetal thymocytes with Wnt1 and Wnt4 results in increased survival in an in vitro cell cultu re system. Retroviral expression of soluble Wnt receptor mutants that block Wnt signaling inhibits thymocyte development. These results imply an impor tant role for the Wnt cascade in thymocyte development.