1. Introduction cytoskeletal connections for cell–ECM contacts. The formation of these regions appears to be a coordinated The organization of any differentiated cell is not random expression of ECM components, cell surface receptors, and but is the result of a dynamic integration of extracellular signaling proteins [1–5]. The localization of fibronectin, and intracellular signals. During the development of the integrins, cadherins, and kinase/phosphotase complexes, heart, cardiac myocytes are round shaped cells that dif- which are all important to myofibrillogenesis, appear as ferentiate into a rod-shaped phenotype. During the differ- focal patches on the myocyte surface (Fig. 2). Interaction ent stages of commitment and morphogenesis, the myocyte with the ECM occurs throughout development; however, organizes its internal structure by undergoing myofibril- the specialization to define the Z bands appears to be logenesis. This process results in the precise arrangement coordinated with myofibrillogenesis and the deposition of of contractile elements, supporting cytoskeleton, and endo- collagen. Fibroblasts appear to secrete collagen that is then plasmic reticulum. Within the sarcolemma, specialized attached to regions on the myocyte where the Z bands are regions are defined for attachment to components of the forming internally [6]. Myofibrillogenesis appears to start extracellular matrix (ECM). This specialized site of the in vivo near the internal margin of the sarcolemma [7, 8]. sarcolemma consists of the ECM–Receptor–Cytoskeleton This observation would be consistent with the presence of complex (Fig. 1). These sites will integrate attachment to specific receptors in the sarcolemma prior to myofibrilthe ECM and the series of proteins necessary for the logenesis necessary for the attachment of the myofibril to chemical and mechanical transmission of information. In the Z band at the same site where collagen is attaching on this review, we will describe the evidence that indicates the outside. These morphological data are consistent with there is a specialization of the sarcolemma at the Z line for the presence of the integrin receptors within the membrane the clustering of various receptors for the ECM as well as at this time [9]. The formation of the collagenous ‘struts’ the cytoskeleton. begins with attachment of a few collagen fibers which appear to increase in number (Fig. 2A). Associated with these attached fibers on the extracellular side are proteo-2. Development of specialized regions of the glycans and glycoproteins [10]. What is not known is how sarcolemma the fibroblast ‘finds’ the myocyte to secrete the collagen at such a precise location. The presence of collagen receptors During development of the embryonic heart, two(integrins) onthemyocyteatthesesitesindicatesthatthese specializedregionsofthesarcolemmadevelop:(1) interca- receptors may play a role in directing collagen strut lated disks for cell–cell interaction and (2) ECM–integrin– formation [11](Fig. 2B). Collagen struts do not appear to attach at precise sites on capillaries, but form a tight weave associated with the basement membrane of the capillary.