Cutting edge: B-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 b-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 b-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 dominantnegative 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.