Regulation of axonal development by natriuretic peptide hormones

Natriuretic peptides (NPs) are a family of cardiac- and vascular-derived hormones that are well known for regulating blood pressure, but their expression in the brain poses an intriguing yet unanswered question concerning their roles in the nervous system. Here, we report several unique activities of these hormones in regulating axonal development of dorsal root ganglion (DRG) neurons in the spinal cord. First, the C-type NP (CNP) is expressed in a restricted area of the dorsal spinal cord and provides a cue that is necessary for bifurcation of central sensory afferents. Second, in the culture of embryonic DRG neurons, CNP stimulates branch formation, induces axon outgrowth, and attracts growth cones. Furthermore, these activities are mediated by cyclic guanosine-3',5'-monophosphate (cGMP) signaling and can be elicited by other members of NP hormones. Thus, NPs represent a new class of extracellular factors that regulate key axonal processes during development. Because their receptors are present in many regions of the embryonic and adult brain, we propose that these hormones have wide influence on the development and function of the nervous system.