Development of the intrinsic and extrinsic innervation of the gut.
The gastrointestinal (GI) tract is innervated by intrinsic enteric neurons and by extrinsic efferent and afferent nerves. The enteric (intrinsic) nervous system (ENS) in most regions of the gut consists of two main ganglionated layers; myenteric and submucosal ganglia, containing numerous types of enteric neurons and glial cells. Axons arising from the ENS and from extrinsic neurons innervate most layers of the gut wall and regulate many gut functions. The majority of ENS cells are derived from vagal neural crest cells (NCCs), which proliferate, colonize the entire gut, and first populate the myenteric region. After gut colonization by vagal NCCs, the extrinsic nerve fibers reach the GI tract, and Schwann cell precursors (SCPs) enter the gut along the extrinsic nerves. Furthermore, a subpopulation of cells in myenteric ganglia undergoes a radial (inward) migration to form the submucosal plexus, and the intrinsic and extrinsic innervation to the mucosal region develops. Here, we focus on recent progress in understanding the developmental processes that occur after the gut is colonized by vagal ENS precursors, and provide an up-to-date overview of molecular mechanisms regulating the development of the intrinsic and extrinsic innervation of the GI tract.
Division of Neural Differentiation and Regeneration, Department of Physiology and Cell Biology, Graduate School of Medicine, Kobe University, Kobe 650-0017, Japan; Laboratory for Neuronal Differentiation and Regeneration, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan; Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan. Electronic address: toshi@phoenix.kobe-u.ac.jp.
Toshihiro
T
Uesaka
Department of Anatomy and Neuroscience, University of Melbourne, 3010 VIC, Australia.
Heather M
HM
Young
Division of Molecular Neurobiology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom.
Vassilis
V
Pachnis
Division of Neural Differentiation and Regeneration, Department of Physiology and Cell Biology, Graduate School of Medicine, Kobe University, Kobe 650-0017, Japan; Laboratory for Neuronal Differentiation and Regeneration, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan; Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan.
Hideki
H
Enomoto
D000818:Animals; D002465:Cell Movement; D017615:Enteric Nervous System / Q000033:anatomy & histology / Q000196:embryology / Q000254:growth & development; D041981:Gastrointestinal Tract / Q000196:embryology / Q000294:innervation*; D006801:Humans; D051379:Mice; D009432:Neural Crest / Q000196:embryology; D055495:Neurogenesis / Q000502:physiology*; D009475:Neurons, Afferent / Q000166:cytology*; D009476:Neurons, Efferent / Q000166:cytology*; D015398:Signal Transduction
Enteric nervous system; Extrinsic nerve innervation; Neuronal and glial differentiation; Neuronal projection; Schwann cell precursors