Pre-TCR-Induced β-Catenin Facilitates Traversal through β-Selection

Abstract

Pre-TCR induced signals regulate development of the αβ TCR lineage cells at the β-selection checkpoint. We have previously shown that conditional deletion of β-catenin, a central mediator of Wnt-β-catenin-T cell factor signaling pathway, impairs traversal through the β-selection checkpoint. We now provide a molecular basis for the impairment. We demonstrate that pre-TCR signals specifically stabilize β-catenin in CD4−CD8− double negative thymocytes during β-selection. Pre-TCR induced Erk activity was required to stabilize β-catenin. Enforced expression of stabilized β-catenin was sufficient to mediate aspects of β-selection including sustained expression of early growth response (Egr) genes. Consistently, deletion of β-catenin reduced induction of Egr gene expression by the pre-TCR signal and blocked efficient β-selection. Thus, we demonstrate that pre-TCR induced β-catenin sustains expression of Egr genes that facilitate traversal through the β-selection checkpoint.