Recent insights into atrial chamber formation.

The sinus node, at the venous end of the heart, automatically generates the electrical impulses that initiate each heart beat and set the heart's rhythm. From the sinus node, these action potentials are transmitted by specialized structures including initially the atrial inner muscle bundles. Congenital malformations of the atrial wall and the corrective procedures used to treat them frequently disrupt atrial physiology, thereby increasing the risk of arrhythmias. Understanding how the atrial inner muscle bundles develop could therefore facilitate therapeutic strategies. Here, we discuss recent findings on the development of the atrial inner wall and contextualize it with the better understood process of ventricular wall development. Atrial wall architecture varies across species, leading to differences in the patterns of action potential propagation and cardiac contractions. More basal vertebrates such as fish and amphibians (e.g., axolotls) display a webbed-like atrial inner myocardium, whereas mammals develop hierarchically patterned atrial inner muscle structures. This architectural evolution may be associated with the higher cardiovascular requirements of homeothermic organisms. Although the complexity of the atrial inner wall appears to be critical for cardiac function, how it emerges has only recently started being investigated. Oriented action potential propagation correlates with the appearance of the first inner muscle bundles in the chick atrium. Recent studies in zebrafish have shown that atrial cardiomyocytes elongate and intercalate to form multilayered inner structures important for optimal cardiac function. Notably, the cellular and molecular mechanisms behind inner wall emergence differ between the atrium and ventricle. Altogether, these findings lay the foundation for future research into atrial morphogenesis and chamber-specific therapies for congenital heart defects.