Neural crest origin of perivascular mesenchyme in the adult thymus.
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.
Müller
Susanna M
SM
Institute for Immunology, University of Ulm, Ulm, Germany.
Stolt
Claus C
CC
Terszowski
Grzegorz
G
Blum
Carmen
C
Amagai
Takashi
T
Kessaris
Nicoletta
N
Iannarelli
Palma
P
Richardson
William D
WD
Wegner
Michael
M
Rodewald
Hans-Reimer
HR
D000818:Animals; D001808:Blood Vessels / Q000196:embryology / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006609:High Mobility Group Proteins / Q000378:metabolism*; D019426:Integrases / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology / Q000196:embryology*; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009432:Neural Crest / Q000166:cytology / Q000196:embryology*; D055757:SOXE Transcription Factors; D013950:Thymus Gland / Q000098:blood supply / Q000166:cytology / Q000196:embryology*; D014157:Transcription Factors / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D055757:SOXE Transcription Factors; C527924:Sox10 protein, mouse; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; C045073:Cre recombinase; D019426:Integrases