The Transcriptional Building Blocks of the Heart

Abstract

Within the adult heart, it is convention to distinguish working myocardium (atrial and ventricular) from conduction system myocardium, each characterized by distinct functional properties and patterns of gene expression [1]. In the tubular heart, expression of most contractile genes such as myosin and actin isoforms show either homogeneous expression or a gradient along the antero-posterior myocardial tube. At this stage, the heart exerts a peristaltoid contraction wave with a posterior-anterior pacemaker polarity. With further development, five different functional cardiac segments can be distinguished [2]. Two fast contracting segments, the atria and ventricles grow out from the outer curvature of the primary heart tube. They are flanked by slow conducting segments reminiscent to the primary cardiac tube, i.e. inflow tract, atrioventricular canal and outflow tract [3]. The ventricles are characterised at this stage by a trabeculated morphology. Eventually, an outer ventricular compact myocardial layer is formed which shows a distinct pattern of gene expression [4]. At this stage, no morphological ventricular conduction system is identifiable albeit that the heart exerts a synchronous contraction wave from apex to the arterial pole. As the heart undergoes septation, each cardiac segment is divided into right and left components. Transgenic mice carrying regulatory sequences of myosin light chain genes have shown a distinct transcriptional potential in right and left atrial and ventricular components [5,6]. The first morphological evidence of a ventricular conduction system can be traced to the fetal stage.