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Blood, 15 August 2005, Vol. 106, No. 4, pp. 1296-1304.
Prepublished online as a Blood First Edition Paper on April 26, 2005; DOI 10.1182/blood-2005-03-0998.


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IMMUNOBIOLOGY

The transcription factor Gli3 regulates differentiation of fetal CD4CD8 double-negative thymocytes

Ariadne L. Hager-Theodorides, Johannes T. Dessens, Susan V. Outram, and Tessa Crompton

From the Division of Cell and Molecular Biology, Faculty of Life Sciences, Imperial College London, London, United Kingdom.

Glioblastoma 3 (Gli3) is a transcription factor involved in patterning and oncogenesis. Here, we demonstrate a role for Gli3 in thymocyte development. Gli3 is differentially expressed in fetal CD4CD8 double-negative (DN) thymocytes and is most highly expressed at the CD44+ CD25 DN (DN1) and CD44–CD25 (DN4) stages of development but was not detected in adult thymocytes. Analysis of null mutants showed that Gli3 is involved at the transitions from DN1 to CD44+ CD25+ DN (DN2) cell and from DN to CD4+CD8+ double-positive (DP) cell. Gli3 is required for differentiation from DN to DP thymocyte, after pre–T-cell receptor (TCR) signaling but is not necessary for pre-TCR–induced proliferation or survival. The effect of Gli3 was dose dependent, suggesting its direct involvement in the transcriptional regulation of genes controlling T-cell differentiation during fetal development.


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