Development of cardiac conduction system in mammals with a focus on the anatomical, functional and medical/genetical aspects

Recent progress in search of mechanisms regulating the spatio-temporal formation of specialized conduction tissues pushes us further in our understanding of the developmental molecular mechanisms of myocardial patterning. It is not clear which mechanisms direct the fates of chamber myocytes to differentiate into ventricular cardiac conduction system (CCS). Similarly, the formation and nature of connections between its most distal component, the Purkinje fibers, and the working myocytes, is unresolved. The process of remodelling of originally ring-like AV junction into AV node and accompanying fibrous insulation between the atria and ventricles is poorly understood, especially on the molecular level. Perturbation of this process can result in abnormal atrio-ventricular connections, manifesting as Wolf-Parkinson-White syndrome of ventricular pre-excitation. Understanding the signalling mechanisms involved in CCS development may be of significance to clinicians and basic researchers studying adult cardiac disease. Congenital abnormalities in CCS, as well as ectopic or inappropriate induction of CCS tissue in the mature heart, may be processes that contribute to, or cause, cardiac conduction disturbance and arrhythmia in adults. Understanding the signalling mechanisms that give rise to normal development of the CCS may thus provide insight into cardiac disease.