Neural Crest Origin of Perivascular Mesenchyme in the Adult Thymus1

The endodermal epithelial thymus anlage develops in tight association with neural crest (NC)-derived mesenchyme. This epithe-lial-NC interaction is crucial for thymus development, but it is not known how NC supports thymus development or whether NC cells or their progeny make any significant contribution to the adult thymus. By nude mouse blastocyst complementation and by cell surface phenotype, we could previously separate thymus stroma into Foxn1-dependent epithelial cells and a Foxn1-indepen-dent mesenchymal cell population. These mesenchymal cells expressed vascular endothelial growth factor-A, and contributed to thymus vascularization. These data suggested a physical or functional association with thymic blood vessels, but the origin, location in the thymus, and function of these stromal cells remained unknown. Using a transgenic mouse expressing Cre recom-binase in premigratory NC (Sox10-Cre), we have now fate-mapped the majority of these adult mesenchymal cells to a NC origin. NC-derived cells represent tightly vessel-associated pericytes that are sandwiched between endothelium and epithelium along the entire thymus vasculature. The ontogenetic, phenotypic, and positional definition of this distinct perivascular mesenchymal com-partment provides a cellular basis for the role of NC in thymus development and possibly maintenance, and might be useful to address properties of the endothelial-epithelial barrier in the adult thymus. The Journal of Immunology, 2008, 180: 5344–5351. T he neural crest (NC)4 generates highly migratory cellsthat contribute in development to diverse cell types, in-cluding neurons and glia and connective tissue such as bone and smooth muscle (1–3). During thymus organogenesis, NC-derived mesenchymal cells colonize the branchial arches an