Staal F J, Meeldijk J, Moerer P, Jay P, van de Weerdt B C, Vainio S, Nolan G P, Clevers H
Department of Immunology and Center for Biomedical Genetics, Utrecht Medical Center, Utrecht, The Netherlands.
Eur J Immunol. 2001 Jan;31(1):285-93. doi: 10.1002/1521-4141(200101)31:1<285::AID-IMMU285>3.0.CO;2-D.
T cell factor / lymphocyte enhancer factor (Tcf/Lef) transcription factors complex with the transcriptional co-activator beta-catenin to transduce Wnt signals in a variety of developmental systems. The prototypic family member Tcf-1 is highly expressed in T lineage cells. Tcf1-/- mice are defective in cell cycling of early thymocyte stages. Here, we show that the interaction of beta-catenin with Tcf-1 is required for full thymocyte development. This interaction may be established by signals mediated by Wnt1 and Wnt4, leading to increased Tcf-dependent transcriptional activity in thymocytes, as demonstrated in Tcf-LacZ reporter mice. Transduction of fetal thymocytes with Wnt1 and Wnt4 results in increased survival in an in vitro cell culture system. Retroviral expression of soluble Wnt receptor mutants that block Wnt signaling inhibits thymocyte development. These results imply an important role for the Wnt cascade in thymocyte development.
T细胞因子/淋巴细胞增强因子（Tcf/Lef）转录因子与转录共激活因子β-连环蛋白形成复合物，以在多种发育系统中传导Wnt信号。该家族的原型成员Tcf-1在T谱系细胞中高度表达。Tcf1-/-小鼠在早期胸腺细胞阶段的细胞周期存在缺陷。在此，我们表明β-连环蛋白与Tcf-1的相互作用是胸腺细胞完全发育所必需的。这种相互作用可能由Wnt1和Wnt4介导的信号建立，导致胸腺细胞中Tcf依赖性转录活性增加，如在Tcf-LacZ报告基因小鼠中所示。用Wnt1和Wnt4转导胎儿胸腺细胞可在体外细胞培养系统中提高存活率。阻断Wnt信号的可溶性Wnt受体突变体的逆转录病毒表达抑制胸腺细胞发育。这些结果表明Wnt级联在胸腺细胞发育中起重要作用。
