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* Institute for Immunology, University of Ulm, Ulm, Germany;
Institute for Biochemistry, University Erlangen-Nürnberg, Erlangen, Germany;
Department of Immunology and Microbiology, Meiji University of Oriental Medicine, Hiyoshi-cho, Funai-gun, Kyoto, Japan; and
Wolfson Institute for Biomedical Research and Department of Biology, University College London, London, United Kingdom
The endodermal epithelial thymus anlage develops in tight association with neural crest (NC)-derived mesenchyme. This epithelial-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-independent 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 recombinase 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 compartment 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 costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 H.-R.R. was supported by grants from the Deutsche Forschungsgemeinschaft (SFB 497-B5 and Klinische Forschergruppe 142-P8).
2 S.M.M., C.C.S., and G.T. made equal contributions to this study.
3 Address correspondence and reprint requests to Dr. Hans-Reimer Rodewald, Institute for Immunology, University of Ulm, D-89081 Ulm. E-mail address: hans-reimer.rodewald{at}uni-ulm.de
4 Abbreviations used in this paper: NC, neural crest; 3rd pp, third pharyngeal pouch; Cnn1, Calponin1; cTEC, cortical thymus epithelial cell; E11.5, embryonic day 11.5; Fgf, fibroblast growth factor; mTEC, medullary thymus epithelial cell; NC-Mes, NC mesenchyme; P0, protein zero; PdgfR, platelet-derived growth factor receptor; Scf, stem cell factor; 
SMA, -smooth muscle actin; TEC, thymus epithelial cell; Vegf-A, vascular endothelial growth factor; wt, wild type; YFP, yellow fluorescent protein.
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  C. Odaka Localization of Mesenchymal Cells in Adult Mouse Thymus: Their Abnormal Distribution in Mice With Disorganization of Thymic Medullary Epithelium J. Histochem. Cytochem., April 1, 2009; 57(4): 373 - 382. [Abstract] [Full Text] [PDF]
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