Autonomic innervation of the developing heart: origins and function.

Maintenance of homeostatic circulation in mammals and birds is reliant upon autonomic innervation of the heart. Neural branches of mixed cellular origin and function innervate the heart at the arterial and venous poles as it matures, eventually coupling autonomic output to the cardiac components, including the conduction system. The development of neural identity is controlled by specific networks of genes and growth factors, whereas functional properties are governed by the use of different neurotransmitters. In this review, we summarize briefly the anatomic arrangement of the vertebrate autonomic nervous system and describe, in detail, the innervation of the heart. We discuss the timing of cardiac innervation in the chick and mouse, emphasizing the relationship of the cardiac neural networks to the anatomical structures within the heart. We also discuss the variable contribution of the neural crest to vagal cardiac nerves, and summarize the main neurotransmitters secreted by the developing sympathetic and parasympathetic autonomic divisions. We provide an overview of the main growth factor and gene families involved in neural development, discussing how these factors may impact upon the development of cardiac abnormalities in congenital syndromes associated with autonomic dysfunction. (c) 2008 Wiley-Liss, Inc.