Multiple transcriptional domains, with distinct left and right components,in the atrial chambers of the developing heart

During heart development, 2 fast-conducting regions of working myocardium b alloon out from the slow-conducting primary myocardium of the tubular heart . Three regions of primary myocardium persist: the outflow tract, atriovent ricular canal, and inflow tract, which are contiguous throughout the inner curvature of the heart. The contribution of the inflow tract to the definit ive atrial chambers has remained enigmatic largely because of the lack of m olecular markers that permit unambiguous identification of this myocardial domain. We now report that the genes encoding atrial natriuretic factor, my osin light chain (MLC) 3F, MLC2V, and Pitx-2, and transgenic mouse lines ex pressing nlacZ under the control of regulatory sequences of the mouse MLC1F /3F gene, display regionalized patterns of expression in the atrial compone nt of the developing mouse heart. These data distinguish 4 broad transcript ional domains in the atrial myocardium: (1) the atrioventricular canal that will form the smooth-walled lower atrial rim proximal to the ventricles; ( 2) the atrial appendages; (3) the caval vein myocardium (systemic inlet); a nd (4) the mediastinal myocardium (pulmonary inlet), including the atrial s epta. The pattern of expression of Pitx-2 reveals that each of these transc riptional domains has a distinct left and right component. This study revea ls for the first time differential gene expression in the systemic and pulm onary inlets, which is not shared by the contiguous atrial appendages and p rovides evidence for multiple molecular compartments within the atrial cham bers. Furthermore, this work will allow the contribution of each of these m yocardial components to be studied in congenitally malformed hearts, such a s those with abnormal venous return.