Sacral neural crest cell migration to the gut is dependent upon the migratory environment and not cell-autonomous migratory properties.

Avian neural crest cells from the vagal (somite level 1-7) and the sacral (somite level 28 and posterior) axial levels migrate into the gut and differentiate into the neurons and glial cells of the enteric nervous system. Neural crest cells that emigrate from the cervical and thoracic levels stop short of the dorsal mesentery and do not enter the gut. In this study we tested the hypothesis that neural crest cells derived from the sacral level have cell-autonomous migratory properties that allow them to reach and invade the gut mesenchyme. We heterotopically grafted neural crest cells from the sacral axial level to the thoracic level and vice versa and observed that the neural crest cells behaved according to their new position, rather than their site of origin. Our results show that the environment at the sacral level is sufficient to allow neural crest cells from other axial levels to enter the mesentery and gut mesenchyme. Our study further suggests that at least two environmental conditions at the sacral level enhance ventral migration. First, sacral neural crest cells take a ventral rather than a medial-to-lateral path through the somites and consequently arrive near the gut mesenchyme many hours earlier than their counterparts at the thoracic level. Our experimental evidence reveals only a narrow window of opportunity to invade the mesenchyme of the mesentery and the gut, so that earlier arrival assures the sacral neural crest of gaining access to the gut. Second, the gut endoderm is more dorsally situated at the sacral level than at the thoracic level. Thus, sacral neural crest cells take a more direct path to the gut than the thoracic neural crest, and also their target is closer to the site from which they initiate migration. In addition, there appears to be a barrier to migration at the thoracic level that prevents neural crest cells at that axial level from migrating ventral to the dorsal aorta and into the mesentery, which is the portal to the gut.