Sculpting organ innervation

Abstract

Neurotrophic growth factors, including nerve growth factor (NGF) and glial-derived neurotrophic factor (GDNF), have well-established roles in promoting the innervation of target tissues, yet little is known about how the temporal and organ-specific expression of these factors is regulated. A new study reveals that NGF is a direct target of the well-characterized peptide factor endothelin-1 (ET-1), and that ET-1-induced NGF expression is required for sympathetic innervation of the developing heart. These results, and recent studies implicating GDNF and ET-3 in the patterning of the enteric nervous system, suggest that specific pairing of endothelins and neurotrophic factors may be used in distinct target organs to coordinate neuronal migration, differentiation, and survival.

Figure 1

Distinctive pairing of endothelins and neurotrophic factors promotes target innervation during development. Although the sequential action of ET-1 to induce myocyte production of NGF is suggested to promote sympathetic innervation of the heart, more complex interactions of ET-3 and GDNF occur in the patterning of the enteric nervous system.