Fig 10. Proposed neurovascular interactions in NCDC migration and enteric sympathetic axon growth.

A: NCDCs migrate along the gut tube immediately following primary vascularization (E10-E13), and never enter a region of the gut prior to the development of a capillary plexus. As this migration occurs prior to angiogenic remodeling and NCDCs do not appear to directly contact capillary endothelial cells, we propose that these endothelial cells may secrete a soluble factor that promotes NCDC migration. B: Sympathetic innervation of the intestine requires two distinct axon guidance stages. From E13-E15, axons extend along intestinal arteries in the mesentery to reach the gut wall. VSMCs in arteries are likely to secrete guidance factors, as has been described in other tissues. C: Upon reaching the gut wall at E15, axons contact the ENS and rapidly spread throughout the enteric ganglia of the myenteric plexus by E17. Enteric neuron-derived netrins have been shown to guide vagal innervation, and a similar mechanism may influence sympathetic guidance within the ENS.