Hierck B P, Poelmann R E, van Iperen L, Brouwer A, Gittenberger-de Groot A C
Department of Anatomy and Embryology, Leiden University, The Netherlands.
Dev Dyn. 1996 May;206(1):100-11. doi: 10.1002/(SICI)1097-0177(199605)206:1<100::AID-AJA9>3.0.CO;2-M.
The development of the heart from a single heart tube to a four chambered organ with two separated unidirectional flows is a highly complex process. Events like looping, septation, tissue remodelling, and development of valves take place in a time period in which the heart already exerts its pump function. Adhesion of cells to each other and to their extracellular matrix as well as the capability to migrate in such a dynamic environment are extremely important. Integrins and extracellular matrix components have already been implicated in this process. In this report, we describe in detail the differential expression of the alpha-6 integrin subunit during late murine heart development, e.g., in the process from looping to the end of septation. We compare mRNA and protein expression patterns with those of beta-1 and other subunits of laminin-binding integrins, alpha-3 and alpha-7. We show a constant and high expression of alpha-6 in the atrial myocardium and a decrease in expression in the ventricular trabecular myocardium. The compact myocardial wall and the ventricular septum do not express alpha-6, except for the myocardium of the distal outflow tract at early stages. Moreover, we describe expression of this integrin subunit in the endocardial cushions that contribute to the development of the atrioventricular and semilunar valves. We propose a role for the alpha-6-beta-1 laminin receptor in the adhesion of cells to their extracellular matrix at sites of high stress due to cardiac contraction or blood flow induced shear stress. Moreover, site specific endothelial expression within the heart and surrounding extracardiac tissue is discussed. This study suggests a distinct role for alpha-6-beta-1 in the heart and provides insight concerning probably important roles of integrins and their extracellular matrix ligands during embryonic development.
心脏从单一的心管发育成为一个具有两个独立单向血流的四腔器官，是一个高度复杂的过程。诸如成环、分隔、组织重塑以及瓣膜发育等事件，都发生在心脏已经发挥其泵功能的时间段内。细胞彼此之间以及与细胞外基质的黏附，以及在这种动态环境中迁移的能力，都极其重要。整合素和细胞外基质成分已经牵涉到这个过程中。在本报告中，我们详细描述了α-6整合素亚基在小鼠心脏发育后期的差异表达，例如在从成环到分隔结束的过程中。我们将mRNA和蛋白质表达模式与β-1以及层粘连蛋白结合整合素的其他亚基α-3和α-7的表达模式进行了比较。我们发现α-6在心房心肌中持续高表达，而在心室小梁心肌中的表达则下降。致密心肌壁和室间隔不表达α-6，除了早期远端流出道的心肌。此外，我们描述了这种整合素亚基在参与房室瓣和半月瓣发育的心内膜垫中的表达。我们提出α-6-β-1层粘连蛋白受体在由于心脏收缩或血流诱导的剪切应力而产生高应力部位的细胞与细胞外基质黏附中发挥作用。此外，还讨论了心脏内以及周围心外组织中位点特异性内皮表达。这项研究表明α-6-β-1在心脏中具有独特作用，并提供了有关整合素及其细胞外基质配体在胚胎发育过程中可能的重要作用的见解。
