Somatic activation of beta-catenin bypasses pre-TCR signaling and TCR selection in thymocyte development.
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 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.
Gounari
F
F
Department of Pathology, Harvard Medical School, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Aifantis
I
I
Khazaie
K
K
Hoeflinger
S
S
Harada
N
N
Taketo
M M
MM
von Boehmer
H
H
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D017209:Apoptosis; D002453:Cell Cycle; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005091:Exons; D005434:Flow Cytometry; D008213:Lymphocyte Activation; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D017384:Sequence Deletion; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000737:chemistry / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology*; D015534:Trans-Activators; D051176:beta Catenin
D000945:Antigens, Differentiation, T-Lymphocyte; C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015534:Trans-Activators; D051176:beta Catenin