The transcription factor Gli3 regulates differentiation of fetal CD4-CD8- double-negative thymocytes
The transcription factor Gli3 regulates differentiation of fetal CD4-CD8- double-negative thymocytes
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DOI：
10.1182/blood-2005-03-0998
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发表时间：
2005-08-15
期刊：
影响因子：
20.3
通讯作者：
Crompton, T
中科院分区：
文献类型：
--
作者：
Hager-Theodorides, AL;Dessens, JT;Crompton, T
胶质母细胞瘤3(Gli3)是一种参与模式形成和肿瘤发生的转录因子。在这里，我们展示了Gli3在胸腺细胞发育中的作用。Gli3在胎儿胸腺细胞中差异表达，在发育的CD44(+)、CD25(-)、DN(DN1)和CD44-CD25(-)(DN4)阶段表达最高，在成人胸腺细胞中未检测到Gli3的表达。对缺失突变体的分析表明，Gli3参与了从DN1到CD44(+)CD25(+)DN(DN2)细胞和从DN到CD4(+)CD8(+)双阳性(DP)细胞的转变。在前T细胞受体(TCR)信号转导之后，Gli3是从糖尿病肾病胸腺细胞分化为DP胸腺细胞所必需的，但不是TCR前诱导的增殖或存活所必需的。Gli3的作用是剂量依赖的，表明它直接参与了胎儿发育过程中控制T细胞分化的基因的转录调控。
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.