The developmentally regulated expression of Twisted gastrulation reveals a role for bone morphogenetic proteins in the control of T cell development
The developmentally regulated expression of Twisted gastrulation reveals a role for bone morphogenetic proteins in the control of T cell development
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DOI：
10.1084/jem.20020276
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发表时间：
2002-07-15
影响因子：
15.3
通讯作者：
Merkenschlager, M
中科院分区：
文献类型：
--
作者：
Graf, D;Nethisinghe, S;Merkenschlager, M
在果蝇和脊椎动物早期胚胎中，进化保守的分泌型蛋白扭曲原肠形成(TSG)调控十五瘫(DPP)及其同源物骨形态发生蛋白2和4(BMP2/4)的形态发生作用。我们已经发现TSG在哺乳动物发育的较晚阶段，在胸腺T细胞分化过程中的作用。BMP4由胸腺基质表达，在体外可抑制CD4(-)CD8(-)双阴性(DN)胸腺细胞的增殖和向CD4(+)CD8(+)双阳性(DP)阶段的分化。TSG由胸腺细胞表达，并在T细胞受体信号传递后在两个发育检查点上调，即从糖尿病肾病过渡到糖尿病肾病和从糖尿病肾病过渡到CD4(+)或CD8(+)单阳性阶段。TSG可与BMP抑制剂Chordin协同作用，阻断BMP4介导的胸腺细胞增殖和分化抑制。这些数据表明，TSG整体调控表达的发展可能允许胸腺细胞暂时退出抑制的BMP信号。
The evolutionarily conserved, secreted protein Twisted gastrulation (Tsg) modulates morphogenetic effects of decapentaplegic (dpp) and its orthologs, the bone morphogenetic proteins 2 and 4 (BMP2/4), in early Drosophila and vertebrate embryos. We have uncovered a role for Tsg at a much later stage of mammalian development, during T cell differentiation in the thymus. BMP4 is expressed by thymic stroma and inhibits the proliferation of CD4(-)CD8(-) double-negative (DN) thymocytes and their differentiation to the CD4(+)CD8(+) double-positive (DP) stage in vitro. Tsg is expressed by thymocytes and up-regulated after T cell receptor signaling at two developmental checkpoints, the transition from the DN to the DP and from the DP to the CD4(+) or CD8(+) single-positive stage. Tsg can synergize with the BMP inhibitor chordin to block the BMP4-mediated inhibition of thymocyte proliferation and differentiation. These data suggest that the develop in en tally regulated expression of Tsg may allow thymocytes to temporarily withdraw from inhibitory, BMP signals.