Essential role of transcriptional regulator Hesl in the early development of T cells.

T细胞在最终匹配前的多个繁殖和差异，在thymus中，一个数字的转录调节器被显示以控制基因激活的distinct步骤。Hes 1，Drosophila Hairy和Split增强剂的哺乳动物对照部分，是基本螺旋-环-螺旋（bHLH）转录调节器的成员，并在正常胚胎中表达了发育中的神经问题和thymus。在神经系统的异常发展中发现了一种罕见的老鼠，以显示出严重的神经系统紊乱。将fetal liver转换为RAG 2 deficient mice指标的实验转移到RAG 2（-1-） fetal liver cells大多完全失败，而B cells和其他红细胞通常被重新固定。Detailed analysis revealed that the differentiation of T cells in thymus from Hes1（-1-） stem cells was arrested at the earliest recognizable stage， CD4-D1-D1 CD4-D1+ D1 CD25-D1-D1 with no evidence of TCR gene rearrangement。结果清楚地表明，Hes 1是一个独立需要的细胞--自动用于thymus中最早的前T细胞扩展。Hes 1显然是在下游的Notch信号路径上进行的，它是由另一个小组报道的，即在成人老鼠中对Thymocyte开发的条件性Notch 1基因目标的类似特定影响。使用适当的细胞系统，我们目前正在研究分子机制，在T细胞发展的具体阶段中控制Hesl的繁殖和差异。

T cells undergo multiple of proliferation and differentiation in the thymus before final maturation, in which a number of transcriptional regulators are shown to control the distinct steps by regulating specific sets of gene activation. Hes 1, a mammalian counterpart of Drosophila Hairy and Enhancer of split, is a member of basic helix-loop-helix (bHLH) transcriptional regulators and expressed in the developing nervous tissues and thymus in normal embryo. Fetus of Hes 1 deficient mice were found to exhibit severe thymus dysplasia in addition of the anomalous development of nervous system. Transfer experiments of fetal liver into RAG2 deficient mice indicate that Hes 1 (-1-) fetal liver cells mostly totally failed to repopulate the thymus while B cells and other hematopoietic cells were reconstituted normally. Detailed analysis revealed that the differentiation of T cells in thymus from Hes 1 (-1-) stem cells was arrested at the earliest recognizable stage, CD4ィイD1-ィエD1CD8ィイD1-ィエD1CD44ィイD1+ィエD1CD25ィイD1-ィエD1 with no evidence of TCR gene rearrangement. The results clearly indicate that Hes 1 is indispensably required cell-autonomously for the earliest expansion of pro-T cells in the thymus. Hes 1 is shown to be at the down-stream of Notch signal pathway, and it was reported by other group that conditional Notch 1 gene targeting in adult mice show similar specific effects on thymocyte development. Using appropriate cell systems, we are currently studying the molecular mechanisms, in which Hesl controls the proliferation and differentiation at the specificstages of T cell development.