Extracellular matrix and heart development

Abstract

The extracellular matrix (ECM) of the developing heart contains numerous molecules that form a dynamic environment that plays an active and crucial role in the regulation of cellular events. ECM molecules found in the heart include hyaluronan, fibronectin, fibrillin, proteoglycans, and collagens. Tight regulation of the spatiotemporal expression, and the proteolytic processing of ECM components by proteases including members of the ADAMTS family, is essential for normal cardiac development. Perturbation of the expression of genes involved in matrix composition and remodeling can interfere with a myriad of events involved in the formation of the four-chambered heart and result in prenatal lethality or cardiac malformations as seen in humans with congenital heart disease. In this review, we summarize what is known about the specific importance of some of the components of the ECM in relation to the cardiovascular development.

Figure 1. Expression of Crtl1, versican, and hyaluronan in the developing atrioventricular cushions of the mouse at ED 13.5

This figure shows transverse serial sections through the AV junction of an ED13.5 wildtype mouse heart. The section in panel A is stained for hematoxylin-eosin. The immunofluorescent stainings in panels B–D demonstrate the overlapping expression of Crtl1 (B), versican (C), and hyaluronan (D) in the AV cushions but also the fact that the mesenchyme of the dorsal mesenchymal protrusion (white arrows) is expressing versican and hyaluronan but not Crtl1. The black arrows in panels C and D point to the muscular component of the interventricular septum in which expression of versican and hyaluronan is also, albeit it at a low level, expressed. iAVC=inferior AV cushion; sAVC=superior AV cushion; llAVC=left lateral AV cushion; rlAVC=right lateral AV cushion; DMP=dorsal mesenchymal protrusion; LA=left atrium; LV=left ventricle; RA=right atrium; RV=right ventricle.

Figure 2. Expression of versican, hyaluronan, and Crtl1 in the developing leaflets of the AV valves at ED 17

This figure shows serial sections through the developing AV valves of a mouse heart at an ED 17 stained for versican (with an antibody recognizing the GAGβ epitope), hyaluronan (using an hyaluronan binding protein HABP approach) and Crtl1. The staining procedures used are essentially as described in Wirrig and others, 2007). Note that the staining for versican is more intense in the leaflets of the developing tricuspid valve when compared to the staining in the aortic and mural leaflet of the mitral valve (A). While versican (A,B) and hyaluronan (C) are still expressed at considerable levels in the tricuspid leaflets, the expression of Crtl1 has significantly decreased at this stage.