Izon David J, Punt Jennifer A, Pear Warren S
TVW Telethon Institute for Child Health Research, Subiaco, WA 6008, Australia.
Curr Opin Immunol. 2002 Apr;14(2):192-9. doi: 10.1016/s0952-7915(02)00321-7.
Components of the Notch signaling pathway are expressed during multiple stages of lymphoid development. Consistent with its function during invertebrate development, Notch signaling is proposed to have a central role in lymphoid cell-fate specification. Recent studies show that Notch signaling is a proximal event in T-cell commitment from a common lymphoid progenitor. The role of Notch at later stages of lymphoid development is controversial, but recent data suggest models that may help clarify observations. Current studies suggest that Notch activity is cell-context dependent and interactions between Notch and other environmental receptors are integrated during cell-fate decisions. Furthermore, the requirement for precise regulation of Notch activity is evident from human and murine neoplasms in which dysregulated Notch signaling leads to T-cell leukemia. Future studies that identify the stages of lymphoid development where Notch signaling is physiologically active and the exact targets of Notch signaling that are relevant to lymphopoiesis should significantly improve our understanding of Notch function in T- and B-cell development.
Notch信号通路的组成部分在淋巴细胞发育的多个阶段均有表达。与其在无脊椎动物发育过程中的功能一致，Notch信号通路被认为在淋巴细胞命运决定中起核心作用。最近的研究表明，Notch信号是普通淋巴祖细胞向T细胞定向分化过程中的一个早期事件。Notch在淋巴细胞发育后期的作用存在争议，但最近的数据提出了一些模型，可能有助于阐明相关观察结果。目前的研究表明，Notch活性取决于细胞环境，并且在细胞命运决定过程中，Notch与其他环境受体之间的相互作用会相互整合。此外，从人类和小鼠肿瘤中可以明显看出对Notch活性进行精确调控的必要性，在这些肿瘤中，Notch信号失调会导致T细胞白血病。未来的研究若能确定Notch信号在生理上活跃的淋巴细胞发育阶段，以及与淋巴细胞生成相关的Notch信号的确切靶点，将显著增进我们对Notch在T细胞和B细胞发育中功能的理解。
