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T cell development and selection require the fully mature and diverse epithelial microenvironment of the thymus. Acquisition of these characteristics is dependent on expression of the forkhead (also known as winged-helix) transcription factor FoxN1, as a lack of functional FoxN1 results in aberrant epithelial morphogenesis and an inability to attract lymphoid precursors to the thymus primordium. However, the transcriptional control of Foxn1 expression has not been elucidated. Here we report that secreted Wnt glycoproteins, expressed by thymic epithelial cells and thymocytes, regulate epithelial Foxn1 expression in both autocrine and paracrine fashions. Wnt molecules therefore provide regulatory signals critical for thymic function.

Original publication

DOI

10.1038/ni850

Type

Journal article

Journal

Nat Immunol

Publication Date

11/2002

Volume

3

Pages

1102 - 1108

Keywords

3T3 Cells, Adaptor Proteins, Signal Transducing, Animals, Autocrine Communication, Cell Differentiation, Chromones, Cytoskeletal Proteins, DNA-Binding Proteins, Dishevelled Proteins, Enzyme Inhibitors, Epithelial Cells, Forkhead Transcription Factors, Gene Expression Regulation, Genes, Reporter, Glycoproteins, Lymphoid Enhancer-Binding Factor 1, Lymphopoiesis, Mice, Mice, Nude, Morphogenesis, Morpholines, Paracrine Communication, Phosphatidylinositol 3-Kinases, Phosphoproteins, Phosphorylation, Protein Biosynthesis, Protein Processing, Post-Translational, Protein-Serine-Threonine Kinases, Proteins, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-akt, Receptors, Cell Surface, Receptors, G-Protein-Coupled, Recombinant Fusion Proteins, T-Lymphocytes, TCF Transcription Factors, Thymus Gland, Trans-Activators, Transcription Factor 7-Like 2 Protein, Transcription Factors, Transcription, Genetic, Wnt Proteins, Wnt3 Protein, Wnt4 Protein, Xenopus Proteins, Zebrafish Proteins, beta Catenin