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Science 315 (5809): 230-233

Copyright © 2007 by the American Association for the Advancement of Science

Regulation of {gamma}{delta} Versus {alpha}ß T Lymphocyte Differentiation by the Transcription Factor SOX13

Heather J. Melichar,1 Kavitha Narayan,1 Sandy D. Der,2 Yoshiki Hiraoka,3 Noemie Gardiol,4 Gregoire Jeannet,4 Werner Held,4 Cynthia A. Chambers,1 Joonsoo Kang1*

Abstract: {alpha}ß and {gamma}{delta} 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 {gamma}{delta}-specific gene in the immune system. Using Sox13 transgenic mice, we showed that this transcription factor promotes {gamma}{delta} T cell development while opposing {alpha}ß T cell differentiation. Conversely, mice deficient in Sox13 expression exhibited impaired development of {gamma}{delta} T cells but not {alpha}ß 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.

1 Department of Pathology, Graduate Program in Immunology and Virology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
2 Department of Laboratory Medicine and Pathobiology, Program in Proteomics and Bioinformatics, University of Toronto, Toronto, Canada.
3 Department of Anatomy, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
4 Ludwig Institute for Cancer Research, Lausanne Branch and University of Lausanne, Chemin Des Boveresses 155, 1066 Epalinges, Switzerland.

* To whom correspondence should be addressed. E-mail: Joonsoo.Kang{at}umassmed.edu


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