Molecular diversity of the developing and adult myocardium: implications for tissue targeting

The heart is the first functional embryonic organ. During embryogenesis the development of the heart and its vasculature is a complex process that give rise to the formation of four-chambered heart with a synchronously contraction, from a single tubular heart with a peristaltic contraction. The spectacular progress of modern developmental biology has marked the beginning of a new era in embryology. Over the last years, several families of genes with restricted cardiac expression have been identified including genes such as those encoding for tissue-specific transcription factors, contractile proteins, as well as, more recently, ion channels. In this review, we illustrate the heterogeneity of the developing and adult myocardium in mice. Looking at the expression profile of transcription factors and contractile proteins, it can be seen that the tubular heart is patterned along the three embryonic axes, antero/posterior, dorso/ventral and left/right, besides having several genes that are expressed homogeneously within the entire myocardium. In the embryonic heart, two new types of pattern arise, chamber-specific and systemic/pulmonary gene expression, while within the foetal and adult heart, a wider heterogeneity is observed, not only between the working myocardium and the specialized cardiac conduction system but also within distinct myocardial chambers, specially in the atrial components. Such heterogeneity is also observed if one looks at the electrophysiological characteristics of the developing myocardium and their underlying molecular components. Several evidences support the notion that the distinct expression profiles observed in mice can be extrapolated to humans. Thus, these data reveal that the molecular diversity of the myocardium should be taken into account on the design of drug targets as well as on gene and cell therapy approaches.