Signalling in T-cell development: is it all location, location, location?

During thymocyte development, signals through the pre-T-cell receptor induce proliferation and differentiation at early stages of maturation; thereafter, signals through the αβ T-cell receptor complex mediate positive and negative selection and commitment to the CD4 or CD8 lineage. How these signals are initiated, the transduction pathways involved, and ultimately how gene transcription is regulated are current active areas of research. Recent literature highlights the importance of geography to thymocyte differentiation: first, in relation to the ability of the developing thymocyte to traffic to localities within the thymus in which particular selection events occur and which are crucial for successful T-cell maturation; and, second, in respect to the subcellular localisation of intracellular signalling molecules, which might provide the key to understanding how similar signals can be translated into dramatically distinct fates, such as positive selection, lineage commitment and negative selection.