Trans-mesenteric neural crest cells are the principal source of the colonic enteric nervous system

Nat Neurosci. 2012 Sep;15(9):1211-8. doi: 10.1038/nn.3184. Epub 2012 Aug 19.


Cell migration is fundamental to organogenesis. During development, the enteric neural crest cells (ENCCs) that give rise to the enteric nervous system (ENS) migrate and colonize the entire length of the gut, which undergoes substantial growth and morphological rearrangement. How ENCCs adapt to such changes during migration, however, is not fully understood. Using time-lapse imaging analyses of mouse ENCCs, we show that a population of ENCCs crosses from the midgut to the hindgut via the mesentery during a developmental time period in which these gut regions are transiently juxtaposed, and that such 'trans-mesenteric' ENCCs constitute a large part of the hindgut ENS. This migratory process requires GDNF signaling, and evidence suggests that impaired trans-mesenteric migration of ENCCs may underlie the pathogenesis of Hirschsprung disease (intestinal aganglionosis). The discovery of this trans-mesenteric ENCC population provides a basis for improving our understanding of ENS development and pathogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Count
  • Cell Movement
  • Colon / embryology*
  • Colon / innervation*
  • Enteric Nervous System / embryology*
  • Enteric Nervous System / physiology*
  • Female
  • Glial Cell Line-Derived Neurotrophic Factor / biosynthesis
  • Glial Cell Line-Derived Neurotrophic Factor / genetics
  • Glial Cell Line-Derived Neurotrophic Factor Receptors / genetics
  • Hirschsprung Disease / genetics
  • Hirschsprung Disease / pathology
  • Humans
  • Immunohistochemistry
  • Magnetic Resonance Imaging
  • Mesentery / cytology
  • Mesentery / embryology*
  • Mesentery / innervation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neural Crest / cytology
  • Neural Crest / physiology*
  • Organ Culture Techniques
  • Polymerase Chain Reaction
  • Pregnancy


  • Gfra1 protein, mouse
  • Glial Cell Line-Derived Neurotrophic Factor
  • Glial Cell Line-Derived Neurotrophic Factor Receptors