The transcription factor Gli3 regulates differentiation of fetal CD4- CD8- double-negative thymocytes.

Blood

Division of Cell and Molecular Biology, Faculty of Life Sciences, Imperial College London, Sir Alexander Fleming Bldg, South Kensington Campus, London SW7 2AZ, United Kingdom.

Published: August 2005

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 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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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1274277PMC
http://dx.doi.org/10.1182/blood-2005-03-0998DOI Listing

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