Enteric neural crest cell migration

Abstract

The formation of a functional enteric nervous system requires the coordination of a complex web of interactions, facilitating the migration, proliferation and differentiation of precursor cells within the gastrointestinal tract. During development, the enteric nervous system is derived from neural crest cells that emigrate from the post‐otic hindbrain ("vagal" level) into and along the developing gut. In mice, vagal neural crest cells enter the developing foregut around E9.5 and migrate rostrocaudally in chains to colonise the entire length of the gut by E14.5. The migration of enteric neural crest cells into and along the gastrointestinal tract is a critical process. Failure of neural crest cells to colonize the entire length of the gastrointestinal tract results in a region of the gut that lacks a functional enteric nervous system. In humans, this condition is called Hirschsprung's disease. Our research is focused on understanding the cellular and molecular mechanisms that influence enteric neural crest cell migration into and along the developing gut. We have shown that the migration of enteric neural crest cells is influenced by multiple factors, including: (i) factors that are secreted by the gut mesenchyme, which regulate the entry of neural crest cells into the gut and promote neural crest cell migration along the gut; and (ii) neural crest cell‐cell interactions, as we have shown that cell‐cell interactions are required for the chain migration of neural crest cells and that changes that altered the equilibrium of these interactions disrupt migration. Together, these studies highlight that enteric neural crest cell migration is a complex process, requiring the integration of multiple factors.