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FGFR2IIIb signaling regulates thymic epithelial differentiation
Author(s) -
Dooley James,
Erickson Matthew,
Larochelle William J.,
Gillard Geoffrey O.,
Farr Andrew G.
Publication year - 2007
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.21364
Subject(s) - fgf10 , biology , thymic involution , microbiology and biotechnology , involution (esoterism) , epithelium , bone marrow , fibroblast growth factor , receptor , endocrinology , immunology , t cell , immune system , genetics , neuroscience , consciousness
Abstract Heterogeneous epithelial populations comprising the thymic environment influence early and late stages of T‐cell development. The processes that regulate the differentiation of thymic epithelium and that are responsible for this heterogeneity are not well understood, although mesenchymal/epithelial interactions are clearly involved. Here, we show that targeted expression by thymocytes of an fibroblast growth factor receptor‐2IIIb (FGFR2IIIb) ligand, FGF10, profoundly alters the differentiation and function of thymic epithelium (TE). Reconstitution of irradiated lck FGF10 mice with normal bone marrow restores normal thymic organization and function, while wild‐type mice reconstituted with lck FGF10 bone marrow recapitulates some of the thymic alterations seen in lck FGF10 mice. We also demonstrate that interference with FGFR2IIIb signaling in the thymus with a soluble FGFR2IIIb dominant‐negative fusion protein leads to precocious reductions in thymic size and cellularity that resemble age‐related thymic involution. These findings indicate that TE compartments are dynamically maintained and that FGF signals are involved in this process. Developmental Dynamics 236:3459–3471, 2007. © 2007 Wiley‐Liss, Inc.