Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
Max Planck Institute for Heart and Lung Research, Department of Developmental Genetics, 61231 Bad Nauheim, Germany.
Development. 2020 Jun 17;147(12):dev185900. doi: 10.1242/dev.185900.
Physical forces are important participants in the cellular dynamics that shape developing organs. During heart formation, for example, contractility and blood flow generate biomechanical cues that influence patterns of cell behavior. Here, we address the interplay between function and form during the assembly of the cardiac outflow tract (OFT), a crucial connection between the heart and vasculature that develops while circulation is under way. In zebrafish, we find that the OFT expands via accrual of both endocardial and myocardial cells. However, when cardiac function is disrupted, OFT endocardial growth ceases, accompanied by reduced proliferation and reduced addition of cells from adjacent vessels. The flow-responsive TGFβ receptor Acvrl1 is required for addition of endocardial cells, but not for their proliferation, indicating distinct modes of function-dependent regulation for each of these essential cell behaviors. Together, our results indicate that cardiac function modulates OFT morphogenesis by triggering endocardial cell accumulation that induces OFT lumen expansion and shapes OFT dimensions. Moreover, these morphogenetic mechanisms provide new perspectives regarding the potential causes of cardiac birth defects.
物理力是塑造发育器官的细胞动力学的重要参与者。例如，在心脏形成过程中，收缩性和血流会产生影响细胞行为模式的生物力学线索。在这里，我们研究了在心脏流出道（OFT）组装过程中功能和形态之间的相互作用，心脏流出道是心脏和脉管系统之间的重要连接，在循环进行的过程中发育。在斑马鱼中，我们发现 OFT 通过心内膜和心肌细胞的积累而扩张。然而，当心脏功能受到干扰时，OFT 心内膜的生长停止，伴随着增殖减少和来自相邻血管的细胞添加减少。响应血流的 TGFβ 受体 Acvrl1 是心内膜细胞添加所必需的，但不是其增殖所必需的，这表明这两种基本细胞行为的功能依赖性调节具有不同的模式。总之，我们的结果表明，心脏功能通过触发心内膜细胞的积累来调节 OFT 的形态发生，从而诱导 OFT 管腔扩张并塑造 OFT 尺寸。此外，这些形态发生机制为心脏先天缺陷的潜在原因提供了新的视角。
