Abstract
The first enteric nervous system (ENS) conference, organized by Marcello Costa and John Furness, was held in Adelaide, Australia in 1983. In this article, we review what was known about the development of the ENS in 1983 and then summarize some of the major advances in the field since 1983.
Keywords
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
The first enteric nervous system (ENS) conference, organized by Marcello Costa and John Furness, was held in Adelaide, Australia in 1983. In this article, we review what was known about the development of the ENS in 1983 and then summarize some of the major advances in the field since 1983.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Anderson RB, Enomoto H, Bornstein JC, Young HM (2004) The enteric nervous system is not essential for the propulsion of gut contents in fetal mice. Gut 53:1546–1547
Anderson RB, Stewart AL, Young HM (2006) Phenotypes of neural-crest-derived cells in vagal and sacral pathways. Cell Tissue Res 323:11–25
Ang SL (2006) Transcriptional control of midbrain dopaminergic neuron development. Development 133:3499–3506
Baetge G, Gershon MD (1989) Transient catecholaminergic (TC) cells in the vagus nerves and bowel of fetal mice: relationship to the development of enteric neurons. Dev Biol 132:189–211
Baetge G, Pintar JE, Gershon MD (1990) Transiently catecholaminergic (TC) cells in the bowel of the fetal rat: precursors of noncatecholaminergic enteric neurons. Dev Biol 141:353–380
Barlow AJ, Wallace AS, Thapar N, Burns AJ (2008) Critical numbers of neural crest cells are required in the pathways from the neural tube to the foregut to ensure complete enteric nervous system formation. Development 135:1681–1691
Bergner AJ et al (2014) Birthdating of myenteric neuron subtypes in the small intestine of the mouse. J Comp Neurol 522:514–527
Blaugrund E et al (1996) Distinct subpopulations of enteric neuronal progenitors defined by time of development, sympathoadrenal lineage markers and Mash-1-dependence. Development 122:309–320
Burns AJ, Le Douarin NM (1998) The sacral neural crest contributes neurons and glia to the post-umbilical gut: spatiotemporal analysis of the development of the enteric nervous system. Development 125:4335–4347
Chalazonitis A (2004) Neurotrophin-3 in the development of the enteric nervous system. Prog Brain Res 146:243–263
Chalazonitis A, Rothman TP, Chen J, Gershon MD (1998) Age-dependent differences in the effects of GDNF and NT-3 on the development of neurons and glia from neural crest-derived precursors immunoselected from the fetal rat gut: expression of GFRalpha-1 in vitro and in vivo. Dev Biol 204:385–406
Chalazonitis A et al (2004) Bone morphogenetic protein-2 and -4 limit the number of enteric neurons but promote development of a TrkC-expressing neurotrophin-3-dependent subset. J Neurosci 24:4266–4282
Chalazonitis A et al (2008) Bone morphogenetic protein regulation of enteric neuronal phenotypic diversity: relationship to timing of cell cycle exit. J Comp Neurol 509:474–492
Chalazonitis A, D’Autreaux F, Pham TD, Kessler JA, Gershon MD (2010) Bone morphogenetic proteins regulate enteric gliogenesis by modulating ErbB3 signaling. Dev Biol 350:64–79
Ciment G, Weston JA (1983) Enteric neurogenesis by neural crest-derived branchial arch mesenchymal cells. Nature 305:424–427
Costa M et al (1996) Neurochemical classification of myenteric neurons in the guinea-pig ileum. Neuroscience 75:949–967
Denaxa M et al (2012) Maturation-promoting activity of SATB1 in MGE-derived cortical interneurons. Cell Rep 2:1351–1362
Druckenbrod NR, Epstein ML (2007) Behavior of enteric neural crest-derived cells varies with respect to the migratory wavefront. Dev Dyn 236:84–92
Druckenbrod NR, Epstein ML (2009) Age-dependent changes in the gut environment restrict the invasion of the hindgut by enteric neural progenitors. Development 136:3195–3203
Durbec P et al (1996) GDNF signalling through the Ret receptor tyrosine kinase. Nature 381:789–793
Edery P et al (1994) Mutations of the RET proto-oncogene in Hirschsprung’s disease. Nature 367:378–380
Epstein ML, Sherman D, Gershon MD (1980) Development of serotonergic neurons in the chick duodenum. Dev Biol 77:22–40
Epstein ML, Hudis J, Dahl JL (1983) The development of peptidergic neurons in the foregut of the chick. J Neurosci 3:2431–2447
Fu M, Lui VC, Sham MH, Pachnis V, Tam PK (2004) Sonic hedgehog regulates the proliferation, differentiation, and migration of enteric neural crest cells in gut. J Cell Biol 166:673–684
Fu M, Vohra BP, Wind D, Heuckeroth RO (2006) BMP signaling regulates murine enteric nervous system precursor migration, neurite fasciculation, and patterning via altered Ncam1 polysialic acid addition. Dev Biol 299:137–150
Fu M et al (2010) Vitamin A facilitates enteric nervous system precursor migration by reducing Pten accumulation. Development 137:631–640
Gershon MD (2010) Developmental determinants of the independence and complexity of the enteric nervous system. Trends Neurosci 33:446–456
Gershon MD, Thompson EB (1973) The maturation of neuromuscular function in a multiply innervated structure: development of the longitudinal smooth muscle of the foetal mammalian gut and its cholinergic excitatory, adrenergic inhibitory, and non-adrenergic inhibitory innervation. J Physiol 234:257–277
Gershon MD, Epstein ML, Hegstrand L (1980) Colonization of the chick gut by progenitors of enteric serotonergic neurons: distribution, differentiation, and maturation within the gut. Dev Biol 77:41–51
Gershon TR et al (2009) Enteric neural crest differentiation in ganglioneuromas implicates Hedgehog signaling in peripheral neuroblastic tumor pathogenesis. PLoS One 4, e7491
Gianino S, Grider JR, Cresswell J, Enomoto H, Heuckeroth RO (2003) GDNF availability determines enteric neuron number by controlling precursor proliferation. Development 130:2187–2198
Goldstein AM, Hofstra RM, Burns AJ (2013) Building a brain in the gut: development of the enteric nervous system. Clin Genet 83:307–316
Goridis C, Brunet JF (1999) Transcriptional control of neurotransmitter phenotype. Curr Opin Neurobiol 9:47–53
Hao MM et al (2011) Early emergence of neural activity in the developing mouse enteric nervous system. J Neurosci 31:15352–15361
Hao MM et al (2012) Early development of electrical excitability in the mouse enteric nervous system. J Neurosci 32:10949–10960
Heanue TA, Pachnis V (2007) Enteric nervous system development and Hirschsprung’s disease: advances in genetic and stem cell studies. Nat Rev Neurosci 8:466–479
Hearn CJ, Murphy M, Newgreen D (1998) GDNF and ET-3 differentially modulate the numbers of avian enteric neural crest cells and enteric neurons in vitro. Dev Biol 197:93–105
Heuckeroth RO, Lampe PA, Johnson EM, Milbrandt J (1998) Neurturin and GDNF promote proliferation and survival of enteric neuron and glial progenitors in vitro. Dev Biol 200:116–129
Howard MJ (2005) Mechanisms and perspectives on differentiation of autonomic neurons. Dev Biol 277:271–286
Jiang Y, Liu MT, Gershon MD (2003) Netrins and DCC in the guidance of migrating neural crest-derived cells in the developing bowel and pancreas. Dev Biol 258:364–384
Kapur RP, Sweetser DA, Doggett B, Siebert JR, Palmiter RD (1995) Intercellular signals downstream of endothelin receptor-B mediate colonization of the large intestine by enteric neuroblasts. Development 121:3787–3795
Kulesa PM, Bailey CM, Kasemeier-Kulesa JC, McLennan R (2010) Cranial neural crest migration: new rules for an old road. Dev Biol 344:543–554
Lake JI, Heuckeroth RO (2013) Enteric nervous system development: migration, differentiation, and disease. Am J Physiol Gastrointest Liver Physiol 305:G1–G24
Lake JI, Tusheva OA, Graham BL, Heuckeroth RO (2013) Hirschsprung-like disease is exacerbated by reduced de novo GMP synthesis. J Clin Invest 123:4875–4887
Lang D et al (2000) Pax3 is required for enteric ganglia formation and functions with Sox10 to modulate expression of c-ret. J Clin Invest 106:963–971
Laranjeira C, Pachnis V (2009) Enteric nervous system development: recent progress and future challenges. Auton Neurosci 151:61–69
Le Douarin NM, Teillet MA (1973) The migration of neural crest cells to the wall of the digestive tract in avian embryo. J Embryol Exp Morphol 30:31–48
Lei J, Howard MJ (2011) Targeted deletion of Hand2 in enteric neural precursor cells affects its functions in neurogenesis, neurotransmitter specification and gangliogenesis, causing functional aganglionosis. Development 138:4789–4800
Li Z et al (2011) Essential roles of enteric neuronal serotonin in gastrointestinal motility and the development/survival of enteric dopaminergic neurons. J Neurosci 31:8998–9009
McConnell SK (1989) The determination of neuronal fate in the cerebral cortex. Trends Neurosci 12:342–349
McKeown SJ, Chow CW, Young HM (2001) Development of the submucous plexus in the large intestine of the mouse. Cell Tissue Res 303:301–305
McLain CR Jr (1963) Amniography studies of the gastrointestinal motility of the human fetus. Am J Obstet Gynecol 86:1079–1087
Moore MW et al (1996) Renal and neuronal abnormalities in mice lacking GDNF. Nature 382:76–79
Mundell NA et al (2012) Enteric nervous system specific deletion of Foxd3 disrupts glial cell differentiation and activates compensatory enteric progenitors. Dev Biol 363:373–387
Nagy N, Goldstein AM (2006) Endothelin-3 regulates neural crest cell proliferation and differentiation in the hindgut enteric nervous system. Dev Biol 293:203–217
Nishiyama C et al (2012) Trans-mesenteric neural crest cells are the principal source of the colonic enteric nervous system. Nat Neurosci 15:1211–1218
Obermayr F, Hotta R, Enomoto H, Young HM (2013) Development and developmental disorders of the enteric nervous system. Nat Rev Gastroenterol Hepatol 10:43–57
Pattyn A, Morin X, Cremer H, Goridis C, Brunet JF (1999) The homeobox gene Phox2b is essential for the development of autonomic neural crest derivatives. Nature 399:366–370
Payette RF, Bennett GS, Gershon MD (1984) Neurofilament expression in vagal neural crest-derived precursors of enteric neurons. Dev Biol 105:273–287
Peters-van der Sanden MJ et al (1993) Ablation of various regions within the avian vagal neural crest has differential effects on ganglion formation in the fore-, mid- and hindgut. Dev Dyn 196:183–194
Pham TD, Gershon MD, Rothman TP (1991) Time of origin of neurons in the murine enteric nervous system: sequence in relation to phenotype. J Comp Neurol 314:789–798
Pichel JG et al (1996) Defects in enteric innervation and kidney development in mice lacking GDNF. Nature 382:73–76
Roberts RR et al (2010) The first intestinal motility patterns in fetal mice are not mediated by neurons or interstitial cells of Cajal. J Physiol 588:1153–1169
Rohrer H (2011) Transcriptional control of differentiation and neurogenesis in autonomic ganglia. Eur J Neurosci 34:1563–1573
Romeo G et al (1994) Point mutations affecting the tyrosine kinase domain of the RET proto-oncogene in Hirschsprung’s disease. Nature 367:377–378
Rothman TP, Gershon MD (1982) Phenotypic expression in the developing murine enteric nervous system. J Neurosci 2:381–393
Sanchez MP et al (1996) Renal agenesis and the absence of enteric neurons in mice lacking GDNF. Nature 382:70–73
Sasselli V, Pachnis V, Burns AJ (2012) The enteric nervous system. Dev Biol 366:64–73
Sasselli V et al (2013) Planar cell polarity genes control the connectivity of enteric neurons. J Clin Invest 123:1763–1772
Schuchardt A, D’Agati V, Larsson-Blomberg L, Costantini F, Pachnis V (1994) Defects in the kidney and enteric nervous system of mice lacking the tyrosine kinase receptor Ret. Nature 367:380–383
Sidebotham EL et al (2002) Localization and endothelin-3 dependence of stem cells of the enteric nervous system in the embryonic colon. J Pediatr Surg 37:145–150
Southard-Smith EM, Kos L, Pavan WJ (1998) Sox10 mutation disrupts neural crest development in Dom Hirschsprung mouse model. Nat Genet 18:60–64
Srinivasan K et al (2012) A network of genetic repression and derepression specifies projection fates in the developing neocortex. Proc Natl Acad Sci U S A 109:19071–19078
Sukegawa A et al (2000) The concentric structure of the developing gut is regulated by Sonic hedgehog derived from endodermal epithelium. Development 127:1971–1980
Taraviras S et al (1999) Signalling by the RET receptor tyrosine kinase and its role in the development of the mammalian enteric nervous system. Development 126:2785–2797
Teitelman G, Gershon MD, Rothman TP, Joh TH, Reis DJ (1981) Proliferation and distribution of cells that transiently express a catecholaminergic phenotype during development of mice and rats. Dev Biol 86:348–355
Teng L, Mundell NA, Frist AY, Wang Q, Labosky PA (2008) Requirement for Foxd3 in the maintenance of neural crest progenitors. Development 135:1615–1624
Theveneau E, Mayor R (2012) Neural crest delamination and migration: from epithelium-to-mesenchyme transition to collective cell migration. Dev Biol 366:34–54
Uesaka T et al (2007) Conditional ablation of GFRalpha1 in postmigratory enteric neurons triggers unconventional neuronal death in the colon and causes a Hirschsprung’s disease phenotype. Development 134:2171–2181
Uesaka T, Nagashimada M, Yonemura S, Enomoto H (2008) Diminished Ret expression compromises neuronal survival in the colon and causes intestinal aganglionosis in mice. J Clin Invest 118:1890–1898
Wallace AS, Burns AJ (2005) Development of the enteric nervous system, smooth muscle and interstitial cells of Cajal in the human gastrointestinal tract. Cell Tissue Res 319:367–382
Wang H et al (2010) The timing and location of glial cell line-derived neurotrophic factor expression determine enteric nervous system structure and function. J Neurosci 30:1523–1538
Wang X, Chan AK, Sham MH, Burns AJ, Chan WY (2011) Analysis of the sacral neural crest cell contribution to the hindgut enteric nervous system in the mouse embryo. Gastroenterology 141:992–1002, e1001–1006
Wu JJ, Chen JX, Rothman TP, Gershon MD (1999) Inhibition of in vitro enteric neuronal development by endothelin-3: mediation by endothelin B receptors. Development 126:1161–1173
Yntema CL, Hammond WS (1954) The origin of intrinsic ganglia of trunk viscera from vagal neural crest in the chick embryo. J Comp Neurol 101:515–541
Young HM et al (2001) GDNF is a chemoattractant for enteric neural cells. Dev Biol 229:503–516
Young HM et al (2004) Dynamics of neural crest-derived cell migration in the embryonic mouse gut. Dev Biol 270:455–473
Young HM et al (2014) Colonizing while migrating: how do individual enteric neural crest cells behave? BMC Biol 12:23
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Young, H.M., Stamp, L.A., McKeown, S.J. (2016). ENS Development Research Since 1983: Great Strides but Many Remaining Challenges. In: Brierley, S., Costa, M. (eds) The Enteric Nervous System. Advances in Experimental Medicine and Biology(), vol 891. Springer, Cham. https://doi.org/10.1007/978-3-319-27592-5_6
Download citation
DOI: https://doi.org/10.1007/978-3-319-27592-5_6
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-27590-1
Online ISBN: 978-3-319-27592-5
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)