Melichar Heather, Kang Joonsoo
Department of Pathology University of Massachusetts Medical School, Worcester, MA 01655, USA.
Immunol Rev. 2007 Feb;215:32-45. doi: 10.1111/j.1600-065X.2006.00469.x.
Morphogens, a class of secreted proteins that regulate gene expression in a concentration-dependent manner, are responsible for directing nearly all lineage fate choices during embryogenesis. In the thymus, morphogen signal pathways consisting of WNT, Hedgehog, and the transforming growth factor-beta superfamily are active and have been implicated in various developmental processes including proliferation, survival, and differentiation of maturing thymocytes. Intriguingly, it has been inferred that some of these morphogen signal pathways differentially affect gammadelta and alphabeta T-cell development or maintenance, but their role in T-cell lineage commitment has not been directly probed. We have recently identified a modulator of morphogen signaling that significantly influences binary gammadelta versus alphabeta T-cell lineage diversification. In this review, we summarize functions of morphogens in the thymus and provide a highly speculative model of integrated morphogen signals, potentially directing the gammadelta versus alphabeta T-cell fate determination process.
形态发生素是一类以浓度依赖方式调节基因表达的分泌蛋白，负责在胚胎发育过程中指导几乎所有的细胞谱系命运选择。在胸腺中，由WNT、刺猬蛋白和转化生长因子-β超家族组成的形态发生素信号通路是活跃的，并且参与了包括成熟胸腺细胞的增殖、存活和分化在内的各种发育过程。有趣的是，据推测这些形态发生素信号通路中的一些会以不同方式影响γδ和αβ T细胞的发育或维持，但它们在T细胞谱系定向中的作用尚未得到直接探究。我们最近鉴定出一种形态发生素信号的调节剂，它对γδ与αβ T细胞谱系的二元分化有显著影响。在这篇综述中，我们总结了形态发生素在胸腺中的功能，并提供了一个极具推测性的整合形态发生素信号模型，该模型可能指导γδ与αβ T细胞命运决定过程。
