Journal
BLOOD
Volume 106, Issue 4, Pages 1296-1304Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2005-03-0998
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Funding
- Wellcome Trust [061000] Funding Source: Medline
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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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