Janssens Sylvie, Van Den Broek Olaf, Davenport Ian R, Akkers Robbert C, Liu Fei, Veenstra Gert Jan C, Hoppler Stefan, Vleminckx Kris, Destrée Olivier
Department of Biomedical Molecular Biology, Ghent University, Belgium.
Int J Dev Biol. 2013;57(1):49-54. doi: 10.1387/ijdb.120191kv.
TCF1 belongs to the family of LEF1/TCF transcription factors that regulate gene expression downstream of Wnt/β-catenin signaling, which is crucial for embryonic development and is involved in adult stem cell regulation and tumor growth. In early Xenopus embryos, tcf1 plays an important role in mesoderm induction and patterning. Foxd3 emerged as a potential tcf1 target gene in a microarray analysis of gastrula stage embryos. Because foxd3 and tcf1 are coexpressed during gastrulation, we investigated whether foxd3 is regulated by tcf1. By using morpholino-mediated knockdown, we show that during gastrulation foxd3 expression is dependent on tcf1. By chromatin immunoprecipitation, we also demonstrate direct interaction of β-catenin/tcf complexes with the foxd3 gene locus. Hence, our results indicate that tcf1 acts as an essential activator of foxd3, which is critical for dorsal mesoderm formation in early embryos.
TCF1属于LEF1/TCF转录因子家族,该家族调控Wnt/β-连环蛋白信号下游的基因表达,这对于胚胎发育至关重要,并参与成体干细胞调控和肿瘤生长。在非洲爪蟾早期胚胎中,tcf1在中胚层诱导和模式形成中发挥重要作用。在原肠胚期胚胎的微阵列分析中,Foxd3作为一个潜在的tcf1靶基因出现。由于foxd3和tcf1在原肠胚形成过程中共同表达,我们研究了foxd3是否受tcf1调控。通过使用吗啉代介导的敲低技术,我们发现原肠胚形成过程中foxd3的表达依赖于tcf1。通过染色质免疫沉淀,我们还证明了β-连环蛋白/tcf复合物与foxd3基因位点的直接相互作用。因此,我们的结果表明tcf1作为foxd3的必需激活因子,这对于早期胚胎中背侧中胚层的形成至关重要。