Trans-mesenteric neural crest cells are the principal source of the colonic enteric nervous system.
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.
Laboratory for Neuronal Differentiation and Regeneration, RIKEN Center for Developmental Biology, Kobe, Japan.
Chihiro
C
Nishiyama
Toshihiro
T
Uesaka
Takayuki
T
Manabe
Yohei
Y
Yonekura
Takashi
T
Nagasawa
Donald F
DF
Newgreen
Heather M
HM
Young
Hideki
H
Enomoto
D000818:Animals; D002452:Cell Count; D002465:Cell Movement; D003106:Colon / Q000196:embryology* / Q000294:innervation*; D017615:Enteric Nervous System / Q000196:embryology* / Q000502:physiology*; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000235:genetics; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors / Q000235:genetics; D006627:Hirschsprung Disease / Q000235:genetics / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008643:Mesentery / Q000166:cytology / Q000196:embryology* / Q000294:innervation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009432:Neural Crest / Q000166:cytology / Q000502:physiology*; D009924:Organ Culture Techniques; D016133:Polymerase Chain Reaction; D011247:Pregnancy
C494988:Gfra1 protein, mouse; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors