Almost 30 years ago pioneering work by the laboratories of Harald von Boehmer and Susumo Tonegawa provided the first indications that developing thymocytes could assemble a functional TCRβ chain-containing receptor complex, the pre-TCR, before TCRα expression. The discovery and study of the pre-TCR complex revealed paradigms of signaling pathways in control of cell survival and proliferation, and culminated in the recognition of the multifunctional nature of this receptor. As a receptor integrated in a dynamic developmental process, the pre-TCR must be viewed not only in the light of the biological outcomes it promotes, but also in context with those molecular processes that drive its expression in thymocytes. This review article focuses on transcription factors and target genes activated by the pre-TCR to drive its different outcomes.

Work in CL-R and JA laboratory has been supported by the Ramón y Cajal and I3 Researchers Programs (CL-R), research grants from the Spanish Government (SAF2009-08066, SAF2012-36535 to CL-R; and BFU2008-01070, SAF2011-24268 to JA), Fundació la Marató TV3 (080730, 122530 to CL-R and JA), the Marie Curie International Reintegration Program of the European Union (MCIRG516308 to CL-R), the Spanish Ministry of Health (ISCIII-RETIC RD06/0009-FEDER), and Generalitat de Catalunya (2009SGR601, 2014SGR1153). CL-R is a recipient of the ICREA Acadèmia Award (Generalitat de Catalunya).