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Signals mediated by the transforming growth factor-beta superfamily of growth factors have been implicated in thymic epithelial cell (TEC) differentiation, homeostasis, and function, but a direct reliance on these signals has not been established. Here we demonstrate that a block in canonical transforming growth factor-beta signaling by the loss of Smad4 expression in TECs leads to qualitative changes in TEC function and a progressively disorganized thymic microenvironment. Moreover, the number of thymus resident early T-lineage progenitors is severely reduced in the absence of Smad4 expression in TECs and directly correlates with extensive thymic and peripheral lymphopenia. Our observations hence place Smad4 within the signaling events in TECs that determine total thymus cellularity by controlling the number of early T-lineage progenitors.

Original publication




Journal article



Publication Date





3688 - 3695


Animals, Base Sequence, Chemokines, DNA, Complementary, Epithelial Cells, Female, Hematopoietic Stem Cells, Homeostasis, Male, Mice, Mice, Mutant Strains, Mice, Transgenic, Pregnancy, Signal Transduction, Smad4 Protein, T-Lymphocytes, Thymus Gland, Transcription, Genetic