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

Nat Immunol. 2001 Sep;2(9):863-9. doi: 10.1038/ni0901-863.

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 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, Differentiation, T-Lymphocyte / analysis
  • Apoptosis
  • Cell Cycle
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism
  • Cytoskeletal Proteins / physiology*
  • Exons
  • Flow Cytometry
  • Lymphocyte Activation
  • Mice
  • Receptors, Antigen, T-Cell / physiology*
  • Receptors, Antigen, T-Cell, alpha-beta / analysis
  • Sequence Deletion
  • Signal Transduction*
  • T-Lymphocytes / chemistry
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • Thymus Gland / immunology*
  • Trans-Activators*
  • beta Catenin

Substances

  • Antigens, Differentiation, T-Lymphocyte
  • CTNNB1 protein, mouse
  • Cytoskeletal Proteins
  • Receptors, Antigen, T-Cell
  • Receptors, Antigen, T-Cell, alpha-beta
  • Trans-Activators
  • beta Catenin