Abstract
alphabeta and gammadelta T cells originate from a common, multipotential precursor population in the thymus, but the molecular mechanisms regulating this lineage-fate decision are unknown. We have identified Sox13 as a gammadelta-specific gene in the immune system. Using Sox13 transgenic mice, we showed that this transcription factor promotes gammadelta T cell development while opposing alphabeta T cell differentiation. Conversely, mice deficient in Sox13 expression exhibited impaired development of gammadelta T cells but not alphabeta T cells. One mechanism of SOX13 function is the inhibition of signaling by the developmentally important Wnt/T cell factor (TCF) pathway. Our data thus reveal a dominant pathway regulating the developmental fate of these two lineages of T lymphocytes.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Autoantigens / genetics
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Autoantigens / metabolism*
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CD4 Antigens / genetics
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Cell Line
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Cell Lineage
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Cell Proliferation
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Embryonic Development
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Gene Expression Profiling
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Gene Expression Regulation
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Gene Rearrangement, T-Lymphocyte
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High Mobility Group Proteins / genetics
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High Mobility Group Proteins / metabolism*
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Humans
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Lymphopoiesis*
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Mice
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Mice, Transgenic
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Receptors, Antigen, T-Cell, alpha-beta / analysis*
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Receptors, Antigen, T-Cell, gamma-delta / analysis*
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Receptors, Antigen, T-Cell, gamma-delta / genetics
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Signal Transduction
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T Cell Transcription Factor 1 / physiology
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T-Lymphocyte Subsets / cytology*
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / metabolism
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Wnt Proteins / metabolism
Substances
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Autoantigens
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CD4 Antigens
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High Mobility Group Proteins
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Receptors, Antigen, T-Cell, alpha-beta
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Receptors, Antigen, T-Cell, gamma-delta
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Sox13 protein, mouse
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T Cell Transcription Factor 1
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Wnt Proteins