Institute of Medical Sciences, Cell and Developmental Biology Research Program, School of Medical Sciences, University of Aberdeen, Aberdeen, Scotland, United Kingdom.
Dev Dyn. 2011 Mar;240(3):649-62. doi: 10.1002/dvdy.22570. Epub 2011 Feb 8.
GATA factors and Wnt signals are key regulators of vertebrate cardiogenesis, but specific roles for individual GATA factors and how they interact with Wnt signaling remain unknown. We use loss of function and overexpression approaches to elucidate how these molecules regulate early cardiogenesis in Xenopus. In order to minimize indirect effects due to abnormal early embryogenesis, we use pluripotent embryonic tissues as cardiogenic assays. We confirm central roles for GATA4, 5, and 6 in cardiogenesis, but also discover individual and different requirements. We show that GATA4 or 6 regulate both cardiogenic potential and subsequent cardiomyocyte differentiation but that GATA5 is involved in regulating cardiomyocyte differentiation. We also show that Wnt11b signaling can rescue reduced cardiac differentiation resulting from loss of function of GATA4 and 6 but not GATA5. We conclude that Wnt11b mediates the differential requirements for GATA factors during vertebrate cardiogenesis.
GATA 因子和 Wnt 信号是脊椎动物心脏发生的关键调节因子，但个别 GATA 因子的具体作用及其与 Wnt 信号的相互作用仍不清楚。我们使用功能丧失和过表达方法来阐明这些分子如何调节非洲爪蟾的早期心脏发生。为了最大限度地减少由于早期胚胎发育异常引起的间接影响，我们使用多能胚胎组织作为心脏发生测定。我们证实 GATA4、5 和 6 在心脏发生中起核心作用，但也发现了各自的不同需求。我们表明 GATA4 或 6 调节心脏发生潜能和随后的心肌细胞分化，但 GATA5 参与调节心肌细胞分化。我们还表明，Wnt11b 信号可以挽救 GATA4 和 6 功能丧失导致的心脏分化减少，但不能挽救 GATA5 功能丧失导致的心脏分化减少。我们的结论是，Wnt11b 介导了脊椎动物心脏发生过程中 GATA 因子的差异需求。
