Development of the thymus requires signaling through the fibroblast growthfactor receptor R2-IIIb

Mice deficient for fibroblast growth factor (Fgf)R2-IIIb show a block in th ymic growth after embryonic day 12.5, a stage that just precedes its detect ion in thymic epithelial cells. Fgf7 and FgflO, the main ligands for FgfR2- IIIb, are expressed in the mesenchyme surrounding the thymic epithelial pri mordium, and Fgf10-deficient mice also exhibit impaired thymic growth. Henc e, Fgf signaling is essential for thymic epithelial proliferation. In addit ion to the proliferative block, most thymic epithelial cells fail to progre ss from an immature cytokeratin 5-positive to a cytokeratin 5-negative phen otype. Nevertheless, sufficient epithelial cell differentiation occurs in t he severely hypoplastic thymus to allow the development of CD4/CD8-double-p ositive thymocytes and a very small number of single-positive thymocytes; e xpressing TCRs. The Journal of Immunology, 2001.