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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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Submitted March 11, 2005
Accepted April 11, 2005
The transcription factor Gli3 regulates differentiation of fetal CD4-CD8-Double Negative thymocytes
Ariadne L Hager-Theodorides, Johannes T Dessens, Susan V Outram, and Tessa Crompton*
Division of Cell and Molecular Biology, Faculty of Life Sciences, Imperial College London, London, United Kingdom
* Corresponding author; email: t.crompton{at}ic.ac.uk.
Glioblastoma (Gli) 3 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 CD4-CD8- 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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