Immunobiology Unit, UCL Institute of Child Health, London, UK.
Cell Cycle. 2010 Oct 15;9(20):4144-52. doi: 10.4161/cc.9.20.13453. Epub 2010 Oct 27.
The Hedgehog (Hh) signaling pathway influences multiple stages of murine T-cell development. Hh signaling mediates transcriptional changes by the activity of the Gli family of transcription factors, Gli1, Gli2 and Gli3. Both Gli2 and Gli3 are essential for mouse development and can be processed to function as transcriptional repressors or transcriptional activators, whereas Gli1, itself a transcriptional target of Hh pathway activation, can only function as a transcriptional activator and is not essential for mouse development. Gli1-deficient mice are healthy and appear normal and nonredundant functions for Gli1 have been difficult to identify. Here we show that Gli1 is non-redundant in the regulation of T-cell development in the thymus, at multiple developmental stages. Analysis of Gli1-deficient embryonic mouse thymus shows a role for Gli1 to promote the differentiation of CD4⁻CD8⁻ double negative (DN) thymocytes before pre- TCR signal transduction, and a negative regulatory function after pre-TCR signaling. In addition, introduction of a Class I-restricted transgenic TCR into the adult Gli1-deficient and embryonic Gli2-deficient thymus showed that both Gli1 and Gli2 influence its selection to the CD8 lineage.
刺猬（Hh）信号通路影响小鼠 T 细胞发育的多个阶段。Hh 信号通过 Gli 家族转录因子Gli1、Gli2 和 Gli3 的活性介导转录变化。Gli2 和 Gli3 对于小鼠的发育都是必不可少的，并且可以被加工成转录抑制因子或转录激活因子，而 Gli1 本身是 Hh 通路激活的转录靶标，只能作为转录激活因子，并且对于小鼠的发育不是必需的。Gli1 缺陷型小鼠是健康的，并且外观正常，Gli1 的非冗余功能难以确定。在这里，我们表明 Gli1 在胸腺 T 细胞发育的多个发育阶段的调控中是非冗余的。对 Gli1 缺陷型胚胎小鼠胸腺的分析表明，Gli1 在 pre-TCR 信号转导之前促进 CD4-CD8-双阴性（DN）胸腺细胞的分化，并且在 pre-TCR 信号之后具有负调节功能。此外，将 Class I 限制性转基因 TCR 引入成年 Gli1 缺陷型和胚胎 Gli2 缺陷型胸腺中表明，Gli1 和 Gli2 都影响其向 CD8 谱系的选择。
