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Abstract

T cells develop in the thymus from precursors that are generated in the bone marrow and continuously seed the thymus through the blood. During evolution, 'outsourcing' the development of one blood lineage, namely the T-cell lineage, to an anatomically distinct hematopoietic organ required the generation of migratory precursors in the bone marrow, their homing to specialized, precursor-retaining thymic niches and their subsequent differentiation. Niche building and precursor homing are therefore intricately linked and should be viewed in context. In this review, we discuss recent findings on the developmental and genetic events that prepare the thymic epithelial microenvironment for its complex tasks, and highlight recent progress in the definition of the thymus-settling cells and the homing process that leads them into the thymus.