enteric nervous system

Summary

Summary: Two ganglionated neural plexuses in the gut wall which form one of the three major divisions of the autonomic nervous system. The enteric nervous system innervates the gastrointestinal tract, the pancreas, and the gallbladder. It contains sensory neurons, interneurons, and motor neurons. Thus the circuitry can autonomously sense the tension and the chemical environment in the gut and regulate blood vessel tone, motility, secretions, and fluid transport. The system is itself governed by the central nervous system and receives both parasympathetic and sympathetic innervation. (From Kandel, Schwartz, and Jessel, Principles of Neural Science, 3d ed, p766)

Top Publications

  1. Van Ginneken C, Schafer K, Van Dam D, Huygelen V, De Deyn P. Morphological changes in the enteric nervous system of aging and APP23 transgenic mice. Brain Res. 2011;1378:43-53 pubmed publisher
    ..In addition, they are frequently occurring co-morbidities in dementia. Whereas a failing enteric nervous system has already been shown to be involved in gastrointestinal motility disorders and in Parkinson's disease, a ..
  2. Metzger M. Neurogenesis in the enteric nervous system. Arch Ital Biol. 2010;148:73-83 pubmed
    The enteric nervous system (ENS) represents the highly organized intrinsic innervation of the gastrointestinal tract and plays a critical role for all stages of postnatal life...
  3. Hackett Jones E, Landman K, Newgreen D, Zhang D. On the role of differential adhesion in gangliogenesis in the enteric nervous system. J Theor Biol. 2011;287:148-59 pubmed publisher
    A defining characteristic of the normal development of the enteric nervous system (ENS) is the existence of mesoscale patterned entities called ganglia...
  4. Gershon M. Behind an enteric neuron there may lie a glial cell. J Clin Invest. 2011;121:3386-9 pubmed publisher
    The enteric nervous system (ENS) controls the gastrointestinal system. Enteric glia have long been regarded as the essential "glue" of the ENS...
  5. Hao M, Moore R, Roberts R, Nguyen T, Furness J, Anderson R, et al. The role of neural activity in the migration and differentiation of enteric neuron precursors. Neurogastroenterol Motil. 2010;22:e127-37 pubmed publisher
    ..i) Some enteric neuron sub-types are present very early during the development of the enteric nervous system. (ii) The rate of differentiation of some sub-types of enteric neurons appears to be influenced by TTX- ..
  6. Wiskur B, Greenwood Van Meerveld B. The aging colon: the role of enteric neurodegeneration in constipation. Curr Gastroenterol Rep. 2010;12:507-12 pubmed publisher
    ..such as Parkinson's disease, not only affect the brain but also cause neurodegeneration within the enteric nervous system leading to colonic dysmotility is presented...
  7. Laranjeira C, Sandgren K, Kessaris N, Richardson W, Potocnik A, Vanden Berghe P, et al. Glial cells in the mouse enteric nervous system can undergo neurogenesis in response to injury. J Clin Invest. 2011;121:3412-24 pubmed publisher
    The enteric nervous system (ENS) in mammals forms from neural crest cells during embryogenesis and early postnatal life...
  8. Nijenhuis C, Ter Horst P, van Rein N, Wilffert B, de Jong van den Berg L. Disturbed development of the enteric nervous system after in utero exposure of selective serotonin re-uptake inhibitors and tricyclic antidepressants. Part 2: Testing the hypotheses. Br J Clin Pharmacol. 2012;73:126-34 pubmed publisher
    ..applied as a proxy for constipation and diarrhoea respectively, which may be associated with disturbed enteric nervous system (ENS) development...
  9. Newgreen D, Dufour S, Howard M, Landman K. Simple rules for a "simple" nervous system? Molecular and biomathematical approaches to enteric nervous system formation and malformation. Dev Biol. 2013;382:305-19 pubmed publisher
    We review morphogenesis of the enteric nervous system from migratory neural crest cells, and defects of this process such as Hirschsprung disease, centering on cell motility and assembly, and cell adhesion and extracellular matrix ..

More Information

Publications62

  1. Buhner S, Schemann M. Mast cell-nerve axis with a focus on the human gut. Biochim Biophys Acta. 2012;1822:85-92 pubmed publisher
    ..On the other hand, mediator release from human intestinal mast cells is modulated by neuropeptides released from enteric and visceral afferent nerves. This article is part of a Special Issue entitled: Mast Cells in Inflammation. ..
  2. Wang X, Chan A, Sham M, Burns A, Chan W. Analysis of the sacral neural crest cell contribution to the hindgut enteric nervous system in the mouse embryo. Gastroenterology. 2011;141:992-1002.e1-6 pubmed publisher
    The majority of the enteric nervous system is derived from the vagal neural crest, with a second contribution, which is restricted to the post-umbilical gut, originating from the sacral neural crest...
  3. O Donnell A, Puri P. A role for Pten in paediatric intestinal dysmotility disorders. Pediatr Surg Int. 2011;27:491-3 pubmed publisher
    The enteric nervous system (ENS) is a network of neurons and glia that lies within the gut wall. It is responsible for the normal regulation of gut motility and secretory activities...
  4. Ngan E, Garcia Barcelo M, Yip B, Poon H, Lau S, Kwok C, et al. Hedgehog/Notch-induced premature gliogenesis represents a new disease mechanism for Hirschsprung disease in mice and humans. J Clin Invest. 2011;121:3467-78 pubmed publisher
    ..Dll1 integrated Hedgehog and Notch pathways to coordinate neuronal and glial cell differentiation during enteric nervous system development...
  5. Hagl C, Wink E, Scherf S, Heumüller Klug S, Hausott B, Schafer K. FGF2 deficit during development leads to specific neuronal cell loss in the enteric nervous system. Histochem Cell Biol. 2013;139:47-57 pubmed publisher
    The largest part of the peripheral nervous system is the enteric nervous system (ENS). It consists of an intricate network of several enteric neuronal subclasses with distinct phenotypes and functions within the gut wall...
  6. Hudson D, Curtis S, Smith V, Griffiths T, Wong A, Scudamore C, et al. Human hephaestin expression is not limited to enterocytes of the gastrointestinal tract but is also found in the antrum, the enteric nervous system, and pancreatic {beta}-cells. Am J Physiol Gastrointest Liver Physiol. 2010;298:G425-32 pubmed publisher
    ..Hp to the entire length of the gastrointestinal tract, the antral portion of the stomach, and to the enteric nervous system (both the myenteric and submucous plexi). Hp was also localized to human pancreatic beta-cells...
  7. Nishino J, Saunders T, Sagane K, Morrison S. Lgi4 promotes the proliferation and differentiation of glial lineage cells throughout the developing peripheral nervous system. J Neurosci. 2010;30:15228-40 pubmed publisher
    ..glioma inactivated 4 (Lgi4) despite the fact that Lgi4 has never been implicated in stem cell function or enteric nervous system development...
  8. Panza E, Knowles C, Graziano C, Thapar N, Burns A, Seri M, et al. Genetics of human enteric neuropathies. Prog Neurobiol. 2012;96:176-89 pubmed publisher
    Knowledge of molecular mechanisms that underlie development of the enteric nervous system has greatly expanded in recent decades. Enteric neuropathies related to aberrant genetic development are thus becoming increasingly recognized...
  9. Ko S, Dass C, Nurgali K. Netrin-1 in the developing enteric nervous system and colorectal cancer. Trends Mol Med. 2012;18:544-54 pubmed publisher
    Netrin-1 is a well-characterised chemoattractant involved in neuronal guidance in the developing enteric nervous system (ENS), but it is also a regulator of tumorigenesis...
  10. Gisser J, Cohen A, Yin H, Gariepy C. A novel bidirectional interaction between endothelin-3 and retinoic acid in rat enteric nervous system precursors. PLoS ONE. 2013;8:e74311 pubmed publisher
    Signaling through the endothelin receptor B (EDNRB) is critical for the development of the enteric nervous system (ENS) and mutations in endothelin system genes cause Hirschsprung's aganglionosis in humans...
  11. Harrington A, Hutson J, Southwell B. Cholinergic neurotransmission and muscarinic receptors in the enteric nervous system. Prog Histochem Cytochem. 2010;44:173-202 pubmed publisher
    There is a rich knowledge of the enteric nervous system (ENS), especially the neurochemical and neurophysiological properties of enteric neurons and how they communicate in neural circuits underlying intestinal reflexes...
  12. Heanue T, Pachnis V. Prospective identification and isolation of enteric nervous system progenitors using Sox2. Stem Cells. 2011;29:128-40 pubmed publisher
    ..The enteric nervous system (ENS) regulates important gut functions, including controlling peristaltic muscular contractions, and ..
  13. Obermayr F, Hotta R, Enomoto H, Young H. Development and developmental disorders of the enteric nervous system. Nat Rev Gastroenterol Hepatol. 2013;10:43-57 pubmed publisher
    The enteric nervous system (ENS) arises from neural crest-derived cells that migrate into and along the gut, leading to the formation of a complex network of neurons and glial cells that regulates motility, secretion and blood flow...
  14. Matsuyoshi H, Kuniyasu H, Okumura M, Misawa H, Katsui R, Zhang G, et al. A 5-HT(4)-receptor activation-induced neural plasticity enhances in vivo reconstructs of enteric nerve circuit insult. Neurogastroenterol Motil. 2010;22:806-13, e226 pubmed publisher
    ..These findings indicate that treatment with 5-HT(4) agonists could be a novel therapy for generating new enteric neurons to rescue aganglionic gut disorders. ..
  15. Stanchina L, Van de Putte T, Goossens M, Huylebroeck D, Bondurand N. Genetic interaction between Sox10 and Zfhx1b during enteric nervous system development. Dev Biol. 2010;341:416-28 pubmed publisher
    ..Hirschsprung disease) respectively, highlighted the importance of both transcription factors during enteric nervous system (ENS) development...
  16. Lakhan S, Kirchgessner A. Neuroinflammation in inflammatory bowel disease. J Neuroinflammation. 2010;7:37 pubmed publisher
    ..in the colonic mucosa in inflammatory bowel disease and signal the presence of inflammation to the enteric nervous system. Inflammatory mediators include 5-hydroxytryptamine and cytokines, as well as reactive oxygen species and ..
  17. Brun P, Giron M, Zoppellaro C, Bin A, Porzionato A, De Caro R, et al. Herpes simplex virus type 1 infection of the rat enteric nervous system evokes small-bowel neuromuscular abnormalities. Gastroenterology. 2010;138:1790-801 pubmed publisher
    ..The release of [(3)H]acetylcholine was reduced significantly in ileum segments after 1 and 6 weeks. After intragastric inoculation, HSV-1 establishes a latent infection in the rat myenteric ganglia, which leads to gut dysmotility. ..
  18. Hotta R, Stamp L, Foong J, McConnell S, Bergner A, Anderson R, et al. Transplanted progenitors generate functional enteric neurons in the postnatal colon. J Clin Invest. 2013;123:1182-91 pubmed publisher
    Cell therapy has the potential to treat gastrointestinal motility disorders caused by diseases of the enteric nervous system. Many studies have demonstrated that various stem/progenitor cells can give rise to functional neurons in the ..
  19. Theocharatos S, Wilkinson D, Darling S, Wilm B, Kenny S, Edgar D. Regulation of progenitor cell proliferation and neuronal differentiation in enteric nervous system neurospheres. PLoS ONE. 2013;8:e54809 pubmed publisher
    b>Enteric nervous system (ENS) progenitor cells isolated from mouse and human bowel can be cultured in vitro as neurospheres which are aggregates of the proliferating progenitor cells, together with neurons and glial cells derived from them...
  20. Bergeron K, Silversides D, Pilon N. The developmental genetics of Hirschsprung's disease. Clin Genet. 2013;83:15-22 pubmed publisher
    ..disease (HSCR), also known as aganglionic megacolon, derives from a congenital malformation of the enteric nervous system (ENS). It displays an incidence of 1 in 5000 live births with a 4:1 male to female sex ratio...
  21. Knowles C, Farrugia G. Gastrointestinal neuromuscular pathology in chronic constipation. Best Pract Res Clin Gastroenterol. 2011;25:43-57 pubmed publisher
    ..Methods with practical diagnostic utility in the individual patient have rarely been employed and require further validation in respect of normative data. ..
  22. Wallace A, Schmidt C, Schachner M, Wegner M, Anderson R. L1cam acts as a modifier gene during enteric nervous system development. Neurobiol Dis. 2010;40:622-33 pubmed publisher
    The enteric nervous system is derived from neural crest cells that migrate from the caudal hindbrain and colonise the gut...
  23. Landman K, Fernando A, Zhang D, Newgreen D. Building stable chains with motile agents: Insights into the morphology of enteric neural crest cell migration. J Theor Biol. 2011;276:250-68 pubmed publisher
    A defining characteristic of the normal development of the enteric nervous system (ENS) is the existence of an enteric neural crest (ENC) cell colonization wave, where the ENC cells form stable chains often associated with axons and near ..
  24. Wood J. Visceral pain: spinal afferents, enteric mast cells, enteric nervous system and stress. Curr Pharm Des. 2011;17:1573-5 pubmed
    ..of visceral hypersensitivity and functional abdominal pain of intestinal origin in relation to the enteric nervous system (ENS), spinal sensory neurons and enteric mast cells...
  25. Nagy N, Burns A, Goldstein A. Immunophenotypic characterization of enteric neural crest cells in the developing avian colorectum. Dev Dyn. 2012;241:842-51 pubmed publisher
    The enteric nervous system (ENS) develops from neural crest-derived cells that migrate along the intestine to form two plexuses of neurons and glia...
  26. Kawaguchi J, Nichols J, Gierl M, Faial T, Smith A. Isolation and propagation of enteric neural crest progenitor cells from mouse embryonic stem cells and embryos. Development. 2010;137:693-704 pubmed publisher
    ..Finally, the demonstration of robust enteric neurogenesis provides a system for investigating and modelling cell therapeutic approaches to neurocristopathies such as Hirschsprung's disease. ..
  27. Freem L, Escot S, Tannahill D, Druckenbrod N, Thapar N, Burns A. The intrinsic innervation of the lung is derived from neural crest cells as shown by optical projection tomography in Wnt1-Cre;YFP reporter mice. J Anat. 2010;217:651-64 pubmed publisher
    ..Our findings demonstrate that intrinsic neurons of the mouse lung are derived from NCCs and that, although implicated in the development of these cells, the role of the RET signalling pathway requires further investigation. ..
  28. Rodrigues D, Li A, Nair D, Blennerhassett M. Glial cell line-derived neurotrophic factor is a key neurotrophin in the postnatal enteric nervous system. Neurogastroenterol Motil. 2011;23:e44-56 pubmed publisher
    The enteric nervous system (ENS) continues its structural and functional growth after birth, with formation of ganglia and the innervation of growing smooth muscle...
  29. Lake J, Heuckeroth R. Enteric nervous system development: migration, differentiation, and disease. Am J Physiol Gastrointest Liver Physiol. 2013;305:G1-24 pubmed publisher
    The enteric nervous system (ENS) provides the intrinsic innervation of the bowel and is the most neurochemically diverse branch of the peripheral nervous system, consisting of two layers of ganglia and fibers encircling the ..
  30. Li Z, Caron M, Blakely R, Margolis K, Gershon M. Dependence of serotonergic and other nonadrenergic enteric neurons on norepinephrine transporter expression. J Neurosci. 2010;30:16730-40 pubmed publisher
    ..innervate the bowel express NET, but they are extrinsic and their cell bodies are not components of the enteric nervous system (ENS)...
  31. Wang H, Hughes I, Planer W, Parsadanian A, Grider J, Vohra B, et al. The timing and location of glial cell line-derived neurotrophic factor expression determine enteric nervous system structure and function. J Neurosci. 2010;30:1523-38 pubmed publisher
    Ret signaling is critical for formation of the enteric nervous system (ENS) because Ret activation promotes ENS precursor survival, proliferation, and migration and provides trophic support for mature enteric neurons...
  32. Butler Tjaden N, Trainor P. The developmental etiology and pathogenesis of Hirschsprung disease. Transl Res. 2013;162:1-15 pubmed publisher
    The enteric nervous system is the part of the autonomic nervous system that directly controls the gastrointestinal tract...
  33. Broders Bondon F, Paul Gilloteaux P, Carlier C, Radice G, Dufour S. N-cadherin and ?1-integrins cooperate during the development of the enteric nervous system. Dev Biol. 2012;364:178-91 pubmed publisher
    Cell adhesion controls various embryonic morphogenetic processes, including the development of the enteric nervous system (ENS)...
  34. Derkinderen P, Rouaud T, Lebouvier T, Bruley des Varannes S, Neunlist M, De Giorgio R. Parkinson disease: the enteric nervous system spills its guts. Neurology. 2011;77:1761-7 pubmed publisher
    ..PD) extends well beyond the CNS, also affecting peripheral autonomic neuronal circuits, especially the enteric nervous system (ENS)...
  35. Hotta R, Natarajan D, Burns A, Thapar N. Stem cells for GI motility disorders. Curr Opin Pharmacol. 2011;11:617-23 pubmed publisher
    ..by conventional endoscopy, and in experimental transplantation studies appear capable of generating a neo-Enteric Nervous System. Current initiatives are addressing pre-clinical proof of concept studies in vivo utilising animal models ..
  36. Joseph N, He S, Quintana E, Kim Y, Nunez G, Morrison S. Enteric glia are multipotent in culture but primarily form glia in the adult rodent gut. J Clin Invest. 2011;121:3398-411 pubmed publisher
    It is unclear whether neurogenesis occurs in the adult mammalian enteric nervous system (ENS)...
  37. Sasselli V, Pachnis V, Burns A. The enteric nervous system. Dev Biol. 2012;366:64-73 pubmed publisher
    The enteric nervous system (ENS), the intrinsic innervation of the gastrointestinal tract, consists of numerous types of neurons, and glial cells, that are distributed in two intramuscular plexuses that extend along the entire length of ..
  38. CHALAZONITIS A, Gershon M, Greene L. Cell death and the developing enteric nervous system. Neurochem Int. 2012;61:839-47 pubmed publisher
    This review discusses current knowledge about cell death in the developing enteric nervous system (ENS). It also includes findings about the molecular mechanisms by which such death is mediated...
  39. Ratcliffe E, Fan L, Mohammed T, Anderson M, CHALAZONITIS A, Gershon M. Enteric neurons synthesize netrins and are essential for the development of the vagal sensory innervation of the fetal gut. Dev Neurobiol. 2011;71:362-73 pubmed publisher
    ..Enteric neurons thus synthesize netrins. The extent to which neuronal netrin accounts for the dependence of the vagal sensory innervation on intrinsic neurons, remains to be determined. ..
  40. Uesaka T, Enomoto H. Neural precursor death is central to the pathogenesis of intestinal aganglionosis in Ret hypomorphic mice. J Neurosci. 2010;30:5211-8 pubmed publisher
    ..the migration, proliferation, and survival of the enteric neural crest-derived cells (ENCCs) that form the enteric nervous system (ENS)...
  41. Sasselli V, Boesmans W, Vanden Berghe P, Tissir F, Goffinet A, Pachnis V. Planar cell polarity genes control the connectivity of enteric neurons. J Clin Invest. 2013;123:1763-72 pubmed publisher
    ..of nascent neuronal projections, leading to subtle changes of axonal tract configuration in the mature enteric nervous system (ENS), but profound abnormalities in gastrointestinal motility...
  42. Kleinschmidt S, Nolte I, Hewicker Trautwein M. Structural and functional components of the feline enteric nervous system. Anat Histol Embryol. 2011;40:450-6 pubmed publisher
    Neurohistological and immunohistochemical examinations of the feline enteric nervous system (ENS) were performed by using antibodies against neuron-specific enolase (NSE), phosphorylated neurofilaments (PN), non-phosphorylated ..
  43. Azan G, Low W, Wendelschafer Crabb G, Ikramuddin S, Kennedy W. Evidence for neural progenitor cells in the human adult enteric nervous system. Cell Tissue Res. 2011;344:217-25 pubmed publisher
    Putative neural stem cells have been identified within the enteric nervous system (ENS) of adult rodents and cultured from human myenteric plexus...
  44. Bercik P, Park A, Sinclair D, Khoshdel A, Lu J, Huang X, et al. The anxiolytic effect of Bifidobacterium longum NCC3001 involves vagal pathways for gut-brain communication. Neurogastroenterol Motil. 2011;23:1132-9 pubmed publisher
    ..As B. longum decreases excitability of enteric neurons, it may signal to the central nervous system by activating vagal pathways at the level of the enteric nervous system.
  45. Freem L, Delalande J, Campbell A, Thapar N, Burns A. Lack of organ specific commitment of vagal neural crest cell derivatives as shown by back-transplantation of GFP chicken tissues. Int J Dev Biol. 2012;56:245-54 pubmed publisher
    ..migrate from the hindbrain into the foregut and from there along the gastrointestinal tract to form the enteric nervous system (ENS), the intrinsic innervation of the gut, and into the developing lung buds to form the intrinsic ..
  46. Dinning P, Costa M, Brookes S, Spencer N. Neurogenic and myogenic motor patterns of rabbit proximal, mid, and distal colon. Am J Physiol Gastrointest Liver Physiol. 2012;303:G83-92 pubmed publisher
    ..The regional specificity motor pattern is likely to facilitate orderly transit of colonic content from semi-liquid to solid composition of feces. ..
  47. Bondurand N, Sham M. The role of SOX10 during enteric nervous system development. Dev Biol. 2013;382:330-43 pubmed publisher
    ..to the understanding of its function in neural crest cells (NCC) in general and in the melanocytes and enteric nervous system (ENS) in particular...
  48. Zhu J, Garcia Barcelo M, Tam P, Lui V. HOXB5 cooperates with NKX2-1 in the transcription of human RET. PLoS ONE. 2011;6:e20815 pubmed publisher
    The enteric nervous system (ENS) regulates peristaltic movement of the gut, and abnormal ENS causes Hirschsprung's disease (HSCR) in newborns...
  49. Margolis K, Stevanovic K, Karamooz N, Li Z, Ahuja A, D Autréaux F, et al. Enteric neuronal density contributes to the severity of intestinal inflammation. Gastroenterology. 2011;141:588-98, 598.e1-2 pubmed publisher
    ..of the neuron-specific enolase promoter) or fewer than normal (Hand2(+/-) mice) numbers of neurons in the enteric nervous system. Colitis was induced with trinitrobenzene sulfonic acid or dextran sulfate sodium, and the intensity of ..
  50. Viader A, Wright Jin E, Vohra B, Heuckeroth R, Milbrandt J. Differential regional and subtype-specific vulnerability of enteric neurons to mitochondrial dysfunction. PLoS ONE. 2011;6:e27727 pubmed publisher
    ..Gastrointestinal dysfunction in these disorders is related, at least in part, to defects in the enteric nervous system (ENS)...
  51. Fichter M, Klotz M, Hirschberg D, Waldura B, Schofer O, Ehnert S, et al. Breast milk contains relevant neurotrophic factors and cytokines for enteric nervous system development. Mol Nutr Food Res. 2011;55:1592-6 pubmed publisher
    ..the content of neurotrophic factors and cytokines, which might influence the postnatal development of the enteric nervous system (ENS), was determined in human breast milk...
  52. Fu Y, Peng S, Lin H, Pasricha P, Tang S. 3-D imaging and illustration of mouse intestinal neurovascular complex. Am J Physiol Gastrointest Liver Physiol. 2013;304:G1-11 pubmed publisher
    ..of nerves and blood vessels, standard histology cannot provide a global and associated observation of the enteric nervous system (ENS) and vascular network...
  53. Fu M, Sato Y, Lyons Warren A, Zhang B, KANE M, Napoli J, et al. Vitamin A facilitates enteric nervous system precursor migration by reducing Pten accumulation. Development. 2010;137:631-40 pubmed publisher
    Hirschsprung disease is a serious disorder of enteric nervous system (ENS) development caused by the failure of ENS precursor migration into the distal bowel...