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

F Gounari, I Aifantis, K Khazaie, S Hoeflinger… - Nature …, 2001 - nature.com
F Gounari, I Aifantis, K Khazaie, S Hoeflinger, N Harada, MM Taketo, H Von Boehmer
Nature immunology, 2001nature.com
Mutation or ablation of T cell factor 1 and lymphocyte enhancer factor 1 indicated
involvement of the Wnt pathway in thymocyte development. The central effector of the Wnt
pathway is β-catenin, which undergoes stabilization upon binding of Wnt ligands to frizzled
receptors. We report here that conditional stabilization of β-catenin in immature thymocytes
resulted in the generation of single positive T cells that lacked the αβ TCR and developed in
the absence of pre-TCR signaling and TCR selection. Although active β-catenin induced …
Abstract
Mutation or ablation of T cell factor 1 and lymphocyte enhancer factor 1 indicated involvement of the Wnt pathway in thymocyte development. The central effector of the Wnt pathway is β-catenin, which undergoes stabilization upon binding of Wnt ligands to frizzled receptors. We report here that conditional stabilization of β-catenin in immature thymocytes resulted in the generation of single positive T cells that lacked the αβ TCR and developed in the absence of pre-TCR signaling and TCR selection. Although active β-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 αβ TCR.
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