Study of the Vertebrate MHC Multigene Family During Heart Development

Abstract

In vertebrates such as birds and mammals, looping and septation generate the four-chambered heart. The origin and lineage relationships of cardiac cell types, endocardial endothelia, ventricular myocytes, and atrial myocytes, constitute the tubular heart when it begins rhythmic contraction. Each cardiac cell type is established by lineage diversification of embryonic cells which arise from one of three distinct origins, cardiogenic mesoderm neural crest, or proepicardium. The structural and functional diversity of the striated muscle is reflected by the presence of a variety of myosin isoforms and is composed of two heavy chains and four light chains. A family of MHC genes encodes myosin heavy chains (MHCs). The vertebrate MHC multigene family has been subdivided into fast skeletal muscle and cardiac/slow skeletal muscle subfamilies (Stedman et al., 1990). The type of MHC expressed in a muscle cell defines the specific type of muscle fiber, significantly affects its contractile properties, and serves as an excellent marker for differentiated cardiac and skeletal muscle (Masaki and Yoshizaki, 1974; Moore et al., 1992; Nguyen et al, 1982, Nudel et al., 1980; Reiser et al., 1988; Robbins et al., 1986: Sartore et al., 1978). The expression of each MHC isoform is regulated in tissue-specific and developmental stage-specific ways (Bader et al., 1982; Bandman et al., 1982; Evans et al., 1988; Lompre et al., 1984). At present, 9 distinct chick sarcomeric MHC isoforms have been described at the protein level in the skeletal muscle, atria, ventricles, and conduction system (de Jong et al., 1988; Bandman and Rosser, 2000; Evans et al., 1988; Gonzalez-Sanchez and Bader, 1984, 1985; Zhang et al, 1986). To date, at both the gene and protein levels, atrial (Oana et al., 1995, 1998; Yutzey et al., 1994) and ventricular (Bisaha and Bader, 1991; Machida et al., 2000a; Stewart et al., 1991) MHCs have been characterized well.