Ontogeny of Cardiac Sympathetic Innervation and Its Implications for Cardiac Disease

The vertebrate heart is innervated by the sympathetic and parasympathetic components of the peripheral autonomic nervous system, which regulates its contractile rate and force. Understanding the mechanisms that control sympathetic neuronal growth, differentiation, and innervation of the heart may provide insight into the etiology of cardiac arrhythmogenesis. This review provides an overview of the cell signaling pathways and transcriptional effectors that regulate both the noradrenergic gene program during sympathetic neurogenesis and regional nerve density during cardiac innervation. Recent studies exploring transcriptional regulation of the bHLH transcription factor Hand1 in developing sympathetic neurons are explored, and how the Hand1 sympathetic neuron-specific cis -regulatory element may be used further to assess the contribution of altered sympathetic innervation to human cardiac disease is discussed.