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The Spatial gene is expressed in highly polarized cell types such as testis germ cells, brain neurons and thymic epithelial cells (TEC). Its expression was documented in testis and brain but poorly characterized in thymus. Here, we characterize for the first time Spatial-expressing TEC throughout ontogeny and adult mouse thymus. Spatial is expressed in thymic-fated domain by embryonic day E10.5 and persists in subcapsular, cortical, medullary epithelial cells and in MTS24(+) progenitor TEC. Using mouse strains in which thymocyte development is blocked at various stages, we show that Spatial expression is independent of thymocyte-derived signals during thymus organogenesis. Analyses on purified thymic cell subsets show that Spatial short isoforms are expressed in cortical TEC (cTEC) and mature medullary TEC (mTEC). Spatial long isoforms were detected in the same TEC population. Spatial presents a nuclear distribution specific to mature mTEC expressing UEA1 and Aire. Aire- and RANKL-deficient mice revealed that Spatial expression is drastically reduced in the thymus of these mutants. These findings reveal a critical function of Aire in regulating Spatial expression, which is compatible with promiscuous Spatial gene expression.

Original publication

DOI

10.1002/eji.200939605

Type

Journal article

Journal

Eur J Immunol

Publication Date

02/2010

Volume

40

Pages

530 - 538

Keywords

Animals, Antigens, Surface, Embryo, Mammalian, Epithelial Cells, Female, Gene Expression Regulation, Developmental, Immunohistochemistry, In Situ Hybridization, Male, Membrane Glycoproteins, Mice, Mice, Inbred C57BL, Mice, Knockout, Nuclear Proteins, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Thymus Gland, Time Factors, Transcription Factors