αβ and γδ 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 γδ-specific gene in the immune system. Using Sox13 transgenic mice, we showed that this transcription factor promotes γδ T cell development while opposing αβ T cell differentiation. Conversely, mice deficient in Sox13 expression exhibited impaired development of γδ cells but not αβ 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.
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