Cutting Edge: β-Catenin-Interacting Tcf1 Isoforms Are Essential for Thymocyte Survival but Dispensable for Thymic Maturation Transitions

T cell factor 1 (Tcf1) is essential for T cell development; however, it remains controversial whether β-catenin, a known coactivator of Tcf1, has a role. Tcf1 is expressed in multiple isoforms in T lineage cells, with the long isoforms interacting with β-catenin through an N-terminal domain. In this study, we specifically ablated Tcf1 long isoforms in mice (p45−/−mice) to abrogate β-catenin interaction. Although thymic cellularity was diminished in p45−/− mice, transition of thymocytes through the maturation stages was unaffected, with no overt signs of developmental blocks. p45−/− thymocytes showed increased apoptosis and alterations in transcriptome, but these changes were substantially more modest than in thymocytes lacking all Tcf1 isoforms. These data indicate that Tcf1–β-catenin interaction is necessary for promoting thymocyte survival to maintain thymic output. Rather than being dominant-negative regulators, Tcf1 short isoforms are adequate in supporting developing thymocytes to traverse through maturation steps and in regulating the expression of most Tcf1 target genes.