Somatic activation of β-catenin bypasses pre-TCR signaling and TCR selection in thymocyte development

Mutation or ablation of T cell factor I and lymphocyte enhancer factor I indicated involvement of the Wnt pathway in thymocyte development. The central effector of the Wnt pathway is beta -catenin, which undergoes stabilization upon binding of Wnt ligands to frizzled receptors. We report here that conditional stabilization of beta -catenin in immature thymocytes resulted in the generation of single positive T cells that lacked the alpha beta TCR and developed in the absence of pre-TCR signaling and TCR selection. Although active beta -catenin induced differentiation in the absence of TCRs, its action was associated with reduced proliferation and survival when compared to developmental changes induced by the pre-TCR or the alpha beta TCR.