Afouda Boni A, Martin Jennifer, Liu Fei, Ciau-Uitz Aldo, Patient Roger, Hoppler Stefan
Institute of Medical Sciences, Cell and Developmental Biology Research Programme, School of Medical Sciences, University of Aberdeen, Aberdeen, UK.
Development. 2008 Oct;135(19):3185-90. doi: 10.1242/dev.026443. Epub 2008 Aug 20.
Cardiogenesis is inhibited by canonical Wnt/beta-catenin signalling and stimulated by non-canonical Wnt11/JNK signalling, but how these two signalling pathways crosstalk is currently unknown. Here, we show that Wnt/beta-catenin signalling restricts cardiogenesis via inhibition of GATA gene expression, as experimentally reinstating GATA function overrides beta-catenin-mediated inhibition and restores cardiogenesis. Furthermore, we show that GATA transcription factors in turn directly regulate Wnt11 gene expression, and that Wnt11 is required to a significant degree for mediating the cardiogenesis-promoting function of GATA transcription factors. These results demonstrate that GATA factors occupy a central position between canonical and non-canonical Wnt signalling in regulating heart muscle formation.
经典Wnt/β-连环蛋白信号通路抑制心脏发生，而非经典Wnt11/JNK信号通路则刺激心脏发生，但目前尚不清楚这两条信号通路是如何相互作用的。在此，我们表明Wnt/β-连环蛋白信号通路通过抑制GATA基因表达来限制心脏发生，因为实验性地恢复GATA功能可克服β-连环蛋白介导的抑制作用并恢复心脏发生。此外，我们表明GATA转录因子反过来直接调节Wnt11基因表达，并且Wnt11在很大程度上是介导GATA转录因子促进心脏发生功能所必需的。这些结果表明，GATA因子在调节心肌形成的经典和非经典Wnt信号通路之间占据核心地位。
