Mapping precursor movement through the postnatal thymus reveals specific microenvironments supporting defined stages of early lymphoid development

Cellular differentiation is a complex process involving integrated signals for lineage specification, proliferation, endowment of functional capacity, and survival or cell death. During embryogenesis, spatially discrete envir onments regulating these processes are established during the growth of tis sue mass, a process that also results in temporal separation of development al events. In tissues that undergo steady-state postnatal differentiation, another means for inducing spatial and temporal separation of developmental cues must be established. Here we show that in the postnatal thymus, this is achieved by inducing blood-borne precursors to enter the organ in a narr ow region of the perimedullary cortex, followed by outward migration across the cortex before accumulation in the subcapsular zone. Notably, blood pre cursors do not transmigrate the cortex in an undifferentiated state, but ra ther undergo progressive developmental changes during this process, such th at defined precursor stages appear in distinct cortical regions. Identifica tion of these cortical regions, together with existing knowledge regarding the genetic potential of the corresponding lymphoid precursors, sets operat ional boundaries for stromal environments that are likely to induce these d ifferentiative events. We conclude that active cell migration between morph ologically similar but functionally distinct stromal regions is an integral component regulating differentiation and homeostasis in the steady-state t hymus.