All peripheral autonomic neurons arise from neural crest cells that migrate away from the neural tube and navigate to the location where ganglia will form. After differentiating into neurons, their axons then navigate to a variety of targets. During the development of the enteric nervous system,
GDNF appears to play a role in inducing vagal neural crest cells to enter the gut, in retaining neural crest cells within the gut and in promoting the migration of neural crest cells along the gut.
Sema3A regulates the entry of extrinsic axons into the distal hindgut,
netrin-DCC signaling is responsible for the centripetal migration of cells to form the submucosal ganglia within the gut, Slit-Robo signaling prevents trunk level neural crest cells from entering the gut, and
neurturin plays a role in the innervation of the circular muscle layer. During the development of the sympathetic nervous system, the migration of trunk neural crest cells through the somites is influenced by
ephrin-Bs,
Sema3A and F-spondin. The migration of neural crest cells ventrally beyond the somites requires
neuregulin signaling and the clumping of cells into columns adjacent to the dorsal aorta is regulated by
Sema3A. The rostral migration of cells to form the superior cervical ganglion (SCG) and the extension of axons along blood vessels involves artemin signaling through Ret and GFRalpha3, and the entry of sympathetic axons into target tissues involves
neurotrophins and
GDNF. Relatively little is known about the development of parasympathetic ganglia, but
GDNF appears to play a role in the migration of some cranial
ganglion precursors to their correct location, and both
GDNF and
neurturin are involved in the growth of parasympathetic axons into particular targets.