Part and Parcel of the Cardiac Autonomic Nerve System: Unravelling Its Cellular Building Blocks during Development

The autonomic nervous system (cANS) is essential for proper heart function, and complications such as heart failure, arrhythmias and even sudden cardiac death are associated with an altered cANS function. A changed innervation state may underlie (part of) the atrial and ventricular arrhythmias observed after myocardial infarction. In other cardiac diseases, such as congenital heart disease, autonomic dysfunction may be related to disease outcome. This is also the case after heart transplantation, when the heart is denervated. Interest in the origin of the autonomic nerve system has renewed since the role of autonomic function in disease progression was recognized, and some plasticity in autonomic regeneration is evident. As with many pathological processes, autonomic dysfunction based on pathological innervation may be a partial recapitulation of the early development of innervation. As such, insight into the development of cardiac innervation and an understanding of the cellular background contributing to cardiac innervation during different phases of development is required. This review describes the development of the cANS and focuses on the cellular contributions, either directly by delivering cells or indirectly by secretion of necessary factors or cell-derivatives.