E proteins and Notch signaling cooperate to promote T cell lineage specification and commitment.
E proteins and Notch signaling cooperate to promote T cell lineage specification and commitment.
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DOI：
10.1084/jem.20060268
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发表时间：
2006-05-15
期刊：
影响因子：
--
通讯作者：
Murre C
中科院分区：
文献类型：
--
作者：
Ikawa T;Kawamoto H;Goldrath AW;Murre C
螺旋-环-螺旋蛋白E47是B系和T系发育所必需的。在这里，我们证明，在体外E47和Notch信号作用一致，以促进胎儿造血祖细胞的T细胞发育，并抑制发展成自然杀伤细胞和骨髓细胞谱系。与Notch信号传导相关的基因集合的表达被E47激活，并且另外，Notch信号传导和E47在平行途径中起作用以诱导基因表达的T谱系特异性程序。Notch细胞内结构域的增强表达挽救了E2 A缺陷胎儿胸腺细胞T细胞定型阶段的发育停滞最后，我们表明，调节Hes 1表达的Notch信号和E47是惊人的相似，在果蝇感觉发育过程中观察到的。基于这些观察结果，我们提出，在发展中的胎儿胸腺细胞E47的行为，以诱导表达的一个合奏的基因参与Notch信号，并随后E47的行为与Notch信号平行，以促进T-谱系成熟。
The helix-loop-helix protein, E47, is essential for both B- and T-lineage development. Here we demonstrate that in vitro E47 and Notch signaling act in concert to promote T cell development from fetal hematopoieitic progenitors and to restrain development into the natural killer and myeloid cell lineages. The expression of an ensemble of genes associated with Notch signaling is activated by E47, and additionally, Notch signaling and E47 act in parallel pathways to induce a T lineage–specific program of gene expression. Enforced expression of the intracellular domain of Notch rescues the developmental arrest at the T cell commitment stage in E2A-deficient fetal thymocytes. Finally, we demonstrate that regulation of Hes1 expression by Notch signaling and E47 is strikingly similar to that observed during Drosophila melanogaster sensory development. Based on these observations, we propose that in developing fetal thymocytes E47 acts to induce the expression of an ensemble of genes involved in Notch signaling, and that subsequently E47 acts in parallel with Notch signaling to promote T-lineage maturation.
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