Development of the thymus requires signaling through the fibroblast growth factor receptor R2-IIIb.
Mice deficient for fibroblast growth factor (Fgf)R2-IIIb show a block in thymic growth after embryonic day 12.5, a stage that just precedes its detection in thymic epithelial cells. Fgf7 and Fgf10, the main ligands for FgfR2-IIIb, are expressed in the mesenchyme surrounding the thymic epithelial primordium, and Fgf10-deficient mice also exhibit impaired thymic growth. Hence, Fgf signaling is essential for thymic epithelial proliferation. In addition to the proliferative block, most thymic epithelial cells fail to progress from an immature cytokeratin 5-positive to a cytokeratin 5-negative phenotype. Nevertheless, sufficient epithelial cell differentiation occurs in the severely hypoplastic thymus to allow the development of CD4/CD8-double-positive thymocytes and a very small number of single-positive thymocytes expressing TCRs.
Revest
J M
JM
Imperial Cancer Research Fund, London, UK.
Suniara
R K
RK
Kerr
K
K
Owen
J J
JJ
Dickson
C
C
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D046508:Culture Techniques; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D004848:Epithelium / Q000473:pathology; D005260:Female; D051526:Fibroblast Growth Factor 10; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors / Q000096:biosynthesis / Q000235:genetics; D017353:Gene Deletion; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D051764:PAX9 Transcription Factor; D051761:Paired Box Transcription Factors; D020033:Protein Isoforms / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000473:pathology; D013950:Thymus Gland / Q000002:abnormalities / Q000254:growth & development* / Q000276:immunology* / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics
D004268:DNA-Binding Proteins; C496464:Fgf10 protein, mouse; C496454:Fgf7 protein, mouse; D051526:Fibroblast Growth Factor 10; D051764:PAX9 Transcription Factor; D051761:Paired Box Transcription Factors; D020033:Protein Isoforms; D017468:Receptors, Fibroblast Growth Factor; D014157:Transcription Factors; C119756:pax19 protein, invertebrate; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; C496354:Fgfr2 protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D051497:Receptor, Fibroblast Growth Factor, Type 2