Ye Ding, Xie Huaping, Hu Bo, Lin Fang
Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, 1-400 Bowen Science Building, 51 Newton Road, Iowa City, IA 52242-1109, USA.
Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, 1-400 Bowen Science Building, 51 Newton Road, Iowa City, IA 52242-1109, USA
Development. 2015 Sep 1;142(17):2928-40. doi: 10.1242/dev.113944.
Coordination between the endoderm and adjacent cardiac mesoderm is crucial for heart development. We previously showed that myocardial migration is promoted by convergent movement of the endoderm, which itself is controlled by the S1pr2/Gα13 signaling pathway, but it remains unclear how the movements of the two tissues is coordinated. Here, we image live and fixed embryos to follow these movements, revealing previously unappreciated details of strikingly complex and dynamic associations between the endoderm and myocardial precursors. We found that during segmentation the endoderm underwent three distinct phases of movement relative to the midline: rapid convergence, little convergence and slight expansion. During these periods, the myocardial cells exhibited different stage-dependent migratory modes: co-migration with the endoderm, movement from the dorsal to the ventral side of the endoderm (subduction) and migration independent of endoderm convergence. We also found that defects in S1pr2/Gα13-mediated endodermal convergence affected all three modes of myocardial cell migration, probably due to the disruption of fibronectin assembly around the myocardial cells and consequent disorganization of the myocardial epithelium. Moreover, we found that additional cell types within the anterior lateral plate mesoderm (ALPM) also underwent subduction, and that this movement likewise depended on endoderm convergence. Our study delineates for the first time the details of the intricate interplay between the endoderm and ALPM during embryogenesis, highlighting why endoderm movement is essential for heart development, and thus potential underpinnings of congenital heart disease.
内胚层与相邻心脏中胚层之间的协调对于心脏发育至关重要。我们之前表明，内胚层的汇聚运动促进心肌迁移，而内胚层的汇聚运动本身受S1pr2/Gα13信号通路控制，但目前尚不清楚这两种组织的运动是如何协调的。在这里，我们对活体和固定胚胎进行成像以追踪这些运动，揭示了内胚层与心肌前体细胞之间惊人复杂且动态关联的先前未被认识到的细节。我们发现，在体节形成期间，内胚层相对于中线经历了三个不同的运动阶段：快速汇聚、几乎不汇聚和轻微扩张。在这些时期，心肌细胞表现出不同阶段依赖的迁移模式：与内胚层共同迁移、从内胚层的背侧向腹侧移动（内陷）以及独立于内胚层汇聚的迁移。我们还发现，S1pr2/Gα13介导的内胚层汇聚缺陷影响了心肌细胞迁移的所有三种模式，这可能是由于心肌细胞周围纤连蛋白组装的破坏以及随之而来的心肌上皮的紊乱。此外，我们发现前外侧板中胚层（ALPM）内的其他细胞类型也经历了内陷，并且这种运动同样依赖于内胚层汇聚。我们的研究首次描绘了胚胎发育过程中内胚层与ALPM之间复杂相互作用的细节，突出了内胚层运动对心脏发育至关重要的原因，以及先天性心脏病的潜在基础。
