Abstract:
Abnormal cardiac development is intimately associated with congenital heart disease. During development, a sponge-like network of muscle fibers in the endocardium, known as trabeculation, becomes compacted. Biomechanical forces regulate myocardial differentiation and proliferation to form trabeculation, while the molecular mechanism is still enigmatic. Biomechanical forces, including intracardiac hemodynamic flow and myocardial contractile force, activate a host of molecular signaling pathways to mediate cardiac morphogenesis. While mechanotransduction pathways to initiate ventricular trabeculation is well studied, deciphering the relative importance of hemodynamic shear vs. mechanical contractile forces to modulate the transition from trabeculation to compaction requires advanced imaging tools and genetically tractable animal models. For these reasons, the advent of 4-D multi-scale light-sheet imaging and complementary multiplex live imaging via micro-CT in the beating zebrafish heart and live chick embryos respectively. Thus, this review highlights the complementary animal models and advanced imaging needed to elucidate the mechanotransduction underlying cardiac ventricular development.
摘要:
心脏发育异常与先天性心脏病密切相关。在开发过程中,心内膜中的一个海绵状的肌肉纤维网络,被称为小梁,变得紧凑。生物力学力调节心肌分化和增殖形成小梁,而分子机制仍然是神秘的。生物力学力,包括心内血流动力学血流和心肌收缩力,激活一系列分子信号通路来介导心脏形态发生。虽然对启动心室小梁形成的机械传导途径进行了充分的研究,破译血液动力学切变与血液动力学切变的相对重要性机械收缩力来调节从小梁形成到压实的转变需要先进的成像工具和遗传可处理的动物模型。由于这些原因,分别在跳动的斑马鱼心脏和活的小鸡胚胎中通过micro-CT进行4-D多尺度光片成像和互补的多重实时成像的出现。因此,本综述重点介绍了阐明心脏心室发育背后的机械传导所需的补充动物模型和先进的影像学检查.