Regulation of gammadelta versus alphabeta T lymphocyte differentiation by the transcription factor SOX13

Heather J Melichar, Kavitha Narayan, Sandy D Der, Yoshiki Hiraoka, Noemie Gardiol, Gregoire Jeannet, Werner Held, Cynthia A Chambers, Joonsoo Kang
Science 2007 January 12, 315 (5809): 230-3
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.


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