Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3 Cells
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Adaptor Proteins, Signal Transducing
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Animals
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Autocrine Communication
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Cell Differentiation
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Chromones / pharmacology
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Cytoskeletal Proteins / biosynthesis
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Cytoskeletal Proteins / genetics
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DNA-Binding Proteins / biosynthesis*
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DNA-Binding Proteins / deficiency
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DNA-Binding Proteins / genetics
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Dishevelled Proteins
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Enzyme Inhibitors / pharmacology
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Epithelial Cells / metabolism
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Epithelial Cells / ultrastructure
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Forkhead Transcription Factors
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Frizzled Receptors
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Gene Expression Regulation*
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Genes, Reporter
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Glycoproteins / biosynthesis
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Glycoproteins / genetics
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Glycoproteins / physiology*
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Lymphoid Enhancer-Binding Factor 1
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Lymphopoiesis / genetics*
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Mice
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Mice, Nude
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Morphogenesis
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Morpholines / pharmacology
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Paracrine Communication
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Phosphatidylinositol 3-Kinases / physiology
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Phosphoinositide-3 Kinase Inhibitors
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Phosphoproteins / biosynthesis
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Phosphoproteins / genetics
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Phosphorylation
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Protein Biosynthesis
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Protein Processing, Post-Translational
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Protein Serine-Threonine Kinases*
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Proteins / genetics
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Proteins / physiology*
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Proto-Oncogene Proteins / biosynthesis
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins / physiology*
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Proto-Oncogene Proteins c-akt
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Receptors, Cell Surface / biosynthesis
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Receptors, Cell Surface / genetics
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Receptors, G-Protein-Coupled*
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Recombinant Fusion Proteins / physiology
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T-Lymphocytes / cytology*
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TCF Transcription Factors
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Thymus Gland / cytology
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Thymus Gland / metabolism
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Trans-Activators / biosynthesis
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Trans-Activators / genetics
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Transcription Factor 7-Like 2 Protein
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Transcription Factors / biosynthesis*
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Transcription Factors / deficiency
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Transcription Factors / genetics
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Transcription Factors / physiology*
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Transcription, Genetic
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Wnt Proteins
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Wnt3 Protein
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Wnt4 Protein
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Xenopus Proteins*
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Zebrafish Proteins*
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beta Catenin
Substances
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Adaptor Proteins, Signal Transducing
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CTNNB1 protein, mouse
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Chromones
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Cytoskeletal Proteins
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DNA-Binding Proteins
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Dishevelled Proteins
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Enzyme Inhibitors
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FZD8 protein, Xenopus
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Forkhead Transcription Factors
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Frizzled Receptors
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Fzd7 protein, mouse
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Glycoproteins
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Lymphoid Enhancer-Binding Factor 1
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Morpholines
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Phosphoinositide-3 Kinase Inhibitors
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Phosphoproteins
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Proteins
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Proto-Oncogene Proteins
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Receptors, Cell Surface
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Receptors, G-Protein-Coupled
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Recombinant Fusion Proteins
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TCF Transcription Factors
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TCF7L2 protein, human
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Tcf7l2 protein, mouse
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Trans-Activators
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Transcription Factor 7-Like 2 Protein
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Transcription Factors
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WNT10B protein, human
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WNT4 protein, human
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Whn protein
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Wnt Proteins
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Wnt10b protein, mouse
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Wnt3 Protein
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Wnt4 Protein
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Wnt4 protein, Xenopus
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Wnt4 protein, mouse
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Wnt5b protein, mouse
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Xenopus Proteins
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Zebrafish Proteins
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beta Catenin
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tcf7l2 protein, Xenopus
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2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt