Inactivation of Notch2 impairs VDJβ rearrangement and allows pre-TCR-independent survival of early αβ lineage thymocytes
Inactivation of Notch2 impairs VDJβ rearrangement and allows pre-TCR-independent survival of early αβ lineage thymocytes
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DOI：
10.1016/s1074-7613(02)00330-8
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发表时间：
2002-06-01
期刊：
影响因子：
32.4
通讯作者：
Radtke, F
中科院分区：
文献类型：
--
作者：
Wolfer, A;Wilson, A;Radtke, F
Noch蛋白在许多发育系统中影响细胞命运的决定。在淋巴发育过程中，Notch1信号对于引导T/B双功能前体走向T细胞的命运至关重要，但Notch1在T细胞发育后期的作用仍存在争议。我们最近报道，在未成熟的(CD44(-)CD25(+))胸腺细胞中，组织特异性的Notch1失活不会影响随后的T细胞发育。在这里，我们证明了在早期(CD44(+)CD25(+))发育阶段Notch1信号的丢失会导致UP而不是Gammadelta谱系发育的严重扰动。未成熟的Notch1(-/-)胸腺细胞表现出VDJβ重排受损和异常的前TCR非依赖性存活。总体而言，我们的数据表明Notch1控制着Alphabeta血统发育所必需的几个非冗余功能。
Notch proteins influence cell fate decisions in many developmental systems. During lymphoid development, Notch1 signaling is essential to direct a bipotent T/B precursor toward the T cell fate, but the role of Notch1 at later stages of T cell development remains controversial. We have recently reported that tissue-specific inactivation of Notch1 in immature (CD44(-)CD25(+)) thymocytes does not affect subsequent T cell development. Here, we demonstrate that loss of Notch1 signaling at an earlier (CD44(+)CD25(+)) developmental stage results in severe perturbation of up but not gammadelta lineage development. Immature Notch1(-/-) thymocytes show impaired VDJbeta rearrangement and aberrant pre-TCR-independent survival. Collectively, our data demonstrate that Notch1 controls several nonredundant functions necessary for alphabeta lineage development.