Department of Biomedical Engineering, Washington University, St Louis, MO 63130, USA.
Development. 2012 May;139(9):1680-90. doi: 10.1242/dev.073486.
The heart is the first functioning organ to form during development. During gastrulation, the cardiac progenitors reside in the lateral plate mesoderm but maintain close contact with the underlying endoderm. In amniotes, these bilateral heart fields are initially organized as a pair of flat epithelia that move towards the embryonic midline and fuse above the anterior intestinal portal (AIP) to form the heart tube. This medial motion is typically attributed to active mesodermal migration over the underlying endoderm. In this model, the role of the endoderm is twofold: to serve as a mechanically passive substrate for the crawling mesoderm and to secrete various growth factors necessary for cardiac specification and differentiation. Here, using computational modeling and experiments on chick embryos, we present evidence supporting an active mechanical role for the endoderm during heart tube assembly. Label-tracking experiments suggest that active endodermal shortening around the AIP accounts for most of the heart field motion towards the midline. Results indicate that this shortening is driven by cytoskeletal contraction, as exposure to the myosin-II inhibitor blebbistatin arrested any shortening and also decreased both tissue stiffness (measured by microindentation) and mechanical tension (measured by cutting experiments). In addition, blebbistatin treatment often resulted in cardia bifida and abnormal foregut morphogenesis. Moreover, finite element simulations of our cutting experiments suggest that the endoderm (not the mesoderm) is the primary contractile tissue layer during this process. Taken together, these results indicate that contraction of the endoderm actively pulls the heart fields towards the embryonic midline, where they fuse to form the heart tube.
心脏是发育过程中第一个形成功能的器官。在原肠胚形成过程中，心脏祖细胞位于侧板中胚层，但与下方的内胚层保持密切接触。在羊膜动物中，这些双侧的心脏区域最初组织为一对扁平的上皮细胞，它们向胚胎的中轴移动，并在前方肠门（AIP）上方融合形成心脏管。这种向中线的内侧运动通常归因于下方内胚层上活跃的中胚层迁移。在这个模型中，内胚层的作用是双重的：作为爬行中胚层的机械被动底物，并分泌心脏特化和分化所需的各种生长因子。在这里，我们使用计算建模和鸡胚实验提供了证据，支持在心脏管组装过程中内胚层具有积极的机械作用。标记跟踪实验表明，AIP 周围活跃的内胚层缩短解释了心脏区域向中线的大部分运动。结果表明，这种缩短是由细胞骨架收缩驱动的，因为肌球蛋白-II 抑制剂 blebbistatin 的暴露会阻止任何缩短，并降低组织刚度（通过微压痕测量）和机械张力（通过切割实验测量）。此外，blebbistatin 处理通常导致心裂和异常前肠形态发生。此外，我们切割实验的有限元模拟表明，在这个过程中，内胚层（而不是中胚层）是主要的收缩组织层。总之，这些结果表明，内胚层的收缩主动将心脏区域拉向胚胎的中轴，在那里它们融合形成心脏管。
