Wnt glycoproteins regulate the expression of FoxN1, the gene defective in nude mice.
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.
Balciunaite
Gina
G
Pediatric Immunology, Department of Research and Clinical-biological Sciences, and the Children's Hospital, University of Basel, Basel, Switzerland.
Keller
Marcel P
MP
Balciunaite
Egle
E
Piali
Luca
L
Zuklys
Saulius
S
Mathieu
Yves D
YD
Gill
Jason
J
Boyd
Richard
R
Sussman
Daniel J
DJ
Holländer
Georg A
GA
D016475:3T3 Cells; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D019898:Autocrine Communication; D002454:Cell Differentiation; D002867:Chromones / Q000494:pharmacology; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D000072261:Dishevelled Proteins; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000378:metabolism / Q000648:ultrastructure; D051858:Forkhead Transcription Factors; D051157:Frizzled Receptors; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006023:Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051821:Lymphoid Enhancer-Binding Factor 1; D038041:Lymphopoiesis / Q000235:genetics*; D051379:Mice; D008819:Mice, Nude; D009024:Morphogenesis; D009025:Morpholines / Q000494:pharmacology; D019899:Paracrine Communication; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics; D010766:Phosphorylation; D014176:Protein Biosynthesis; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics; D043562:Receptors, G-Protein-Coupled; D011993:Recombinant Fusion Proteins / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology*; D051820:TCF Transcription Factors; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060528:Wnt4 Protein; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin
D048868:Adaptor Proteins, Signal Transducing; D002867:Chromones; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D000072261:Dishevelled Proteins; D004791:Enzyme Inhibitors; D051858:Forkhead Transcription Factors; D051157:Frizzled Receptors; D006023:Glycoproteins; D051821:Lymphoid Enhancer-Binding Factor 1; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010750:Phosphoproteins; D017346:Protein Serine-Threonine Kinases; D011506:Proteins; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D011993:Recombinant Fusion Proteins; D051820:TCF Transcription Factors; D015534:Trans-Activators; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060528:Wnt4 Protein; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; C495267:CTNNB1 protein, mouse; C113865:FZD8 protein, Xenopus; C492041:Fzd7 protein, mouse; C544894:TCF7L2 protein, human; C544895:Tcf7l2 protein, mouse; C491119:WNT10B protein, human; C555581:WNT4 protein, human; C090140:Whn protein; C102068:Wnt10b protein, mouse; C555584:Wnt4 protein, Xenopus; C555582:Wnt4 protein, mouse; C468567:Wnt5b protein, mouse; C544896:tcf7l2 protein, Xenopus; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one