Enteric Nervous System Development: What Could Possibly Go Wrong?

Overview

Journal Nat Rev Neurosci

Specialty Neurology

Date 2018 Jul 27

PMID 30046054

Citations 77

Authors

Meenakshi Rao

Michael D Gershon

Affiliations

Soon will be listed here.

Abstract

The gastrointestinal tract contains its own set of intrinsic neuroglial circuits - the enteric nervous system (ENS) - which detects and responds to diverse signals from the environment. Here, we address recent advances in the understanding of ENS development, including how neural-crest-derived progenitors migrate into and colonize the bowel, the formation of ganglionated plexuses and the molecular mechanisms of enteric neuronal and glial diversification. Modern lineage tracing and transcription-profiling technologies have produced observations that simultaneously challenge and affirm long-held beliefs about ENS development. We review many genetic and environmental factors that can alter ENS development and exert long-lasting effects on gastrointestinal function, and discuss how developmental defects in the ENS might account for some of the large burden of digestive disease.

Citing Articles

The Gut Microbiota's Role in Neurological, Psychiatric, and Neurodevelopmental Disorders.

Charitos I, Inchingolo A, Ferrante L, Inchingolo F, Inchingolo A, Castellaneta F Nutrients. 2025; 16(24.

PMID: 39771025 PMC: 11677138. DOI: 10.3390/nu16244404.

Roles of the gut microbiota in human neurodevelopment and adult brain disorders.

Mallick R, Basak S, Das R, Banerjee A, Paul S, Pathak S Front Neurosci. 2024; 18:1446700.

PMID: 39659882 PMC: 11628544. DOI: 10.3389/fnins.2024.1446700.

Spatiotemporal dynamics of the developing zebrafish enteric nervous system at the whole-organ level.

Li C, Gehring J, Bronner M Dev Cell. 2024; 60(4):613-629.e6.

PMID: 39642879 PMC: 11859770. DOI: 10.1016/j.devcel.2024.11.006.

Causes and consequences: development and pathophysiology of Hirschsprung disease.

Burns A, Goldstein A World J Pediatr Surg. 2024; 7(4):e000903.

PMID: 39600627 PMC: 11590806. DOI: 10.1136/wjps-2024-000903.

The peripheral neuroimmune system.

Song K, Kim B J Leukoc Biol. 2024; 116(6):1291-1300.

PMID: 39422243 PMC: 11599120. DOI: 10.1093/jleuko/qiae230.

References

Pingault V, Bondurand N, Kuhlbrodt K, Goerich D, Prehu M, Puliti A . SOX10 mutations in patients with Waardenburg-Hirschsprung disease. Nat Genet. 1998; 18(2):171-3. DOI: 10.1038/ng0298-171. View

Zhao X, Pack M . Modeling intestinal disorders using zebrafish. Methods Cell Biol. 2017; 138:241-270. DOI: 10.1016/bs.mcb.2016.11.006. View

Li Z, Schmauss C, Cuenca A, Ratcliffe E, Gershon M . Physiological modulation of intestinal motility by enteric dopaminergic neurons and the D2 receptor: analysis of dopamine receptor expression, location, development, and function in wild-type and knock-out mice. J Neurosci. 2006; 26(10):2798-807. PMC: 6675162. DOI: 10.1523/JNEUROSCI.4720-05.2006. View

Memic F, Knoflach V, Morarach K, Sadler R, Laranjeira C, Hjerling-Leffler J . Transcription and Signaling Regulators in Developing Neuronal Subtypes of Mouse and Human Enteric Nervous System. Gastroenterology. 2017; 154(3):624-636. PMC: 6381388. DOI: 10.1053/j.gastro.2017.10.005. View

Nagashimada M, Ohta H, Li C, Nakao K, Uesaka T, Brunet J . Autonomic neurocristopathy-associated mutations in PHOX2B dysregulate Sox10 expression. J Clin Invest. 2012; 122(9):3145-58. PMC: 3428093. DOI: 10.1172/JCI63401. View

Ibiza S, Garcia-Cassani B, Ribeiro H, Carvalho T, Almeida L, Marques R . Glial-cell-derived neuroregulators control type 3 innate lymphoid cells and gut defence. Nature. 2016; 535(7612):440-443. PMC: 4962913. DOI: 10.1038/nature18644. View

Pham T, Gershon M, Rothman T . Time of origin of neurons in the murine enteric nervous system: sequence in relation to phenotype. J Comp Neurol. 1991; 314(4):789-98. DOI: 10.1002/cne.903140411. View

Lebrand C, Cases O, Wehrle R, Blakely R, EDWARDS R, Gaspar P . Transient developmental expression of monoamine transporters in the rodent forebrain. J Comp Neurol. 1998; 401(4):506-24. View

Burns A, Le Douarin N . In ovo transplantation of enteric nervous system precursors from vagal to sacral neural crest results in extensive hindgut colonisation. Development. 2002; 129(12):2785-96. DOI: 10.1242/dev.129.12.2785. View

10.

Lasrado R, Boesmans W, Kleinjung J, Pin C, Bell D, Bhaw L . Lineage-dependent spatial and functional organization of the mammalian enteric nervous system. Science. 2017; 356(6339):722-726. DOI: 10.1126/science.aam7511. View

11.

Li Z, Pham T, Tamir H, Chen J, Gershon M . Enteric dopaminergic neurons: definition, developmental lineage, and effects of extrinsic denervation. J Neurosci. 2004; 24(6):1330-9. PMC: 6730344. DOI: 10.1523/JNEUROSCI.3982-03.2004. View

12.

Serbedzija G, Fraser S, Bronner-Fraser M . Pathways of trunk neural crest cell migration in the mouse embryo as revealed by vital dye labelling. Development. 1990; 108(4):605-12. DOI: 10.1242/dev.108.4.605. View

13.

Schuchardt A, DAgati V, Costantini F, Pachnis V . Defects in the kidney and enteric nervous system of mice lacking the tyrosine kinase receptor Ret. Nature. 1994; 367(6461):380-3. DOI: 10.1038/367380a0. View

14.

Collins J, Borojevic R, Verdu E, Huizinga J, Ratcliffe E . Intestinal microbiota influence the early postnatal development of the enteric nervous system. Neurogastroenterol Motil. 2013; 26(1):98-107. DOI: 10.1111/nmo.12236. View

15.

Grubisic V, Gulbransen B . Enteric glial activity regulates secretomotor function in the mouse colon but does not acutely affect gut permeability. J Physiol. 2017; 595(11):3409-3424. PMC: 5451715. DOI: 10.1113/JP273492. View

16.

Wallace A, Burns A . Development of the enteric nervous system, smooth muscle and interstitial cells of Cajal in the human gastrointestinal tract. Cell Tissue Res. 2005; 319(3):367-82. DOI: 10.1007/s00441-004-1023-2. View

17.

Hao M, Foong J, Bornstein J, Li Z, Vanden Berghe P, Boesmans W . Enteric nervous system assembly: Functional integration within the developing gut. Dev Biol. 2016; 417(2):168-81. DOI: 10.1016/j.ydbio.2016.05.030. View

18.

de Bellard M, Rao Y, Bronner-Fraser M . Dual function of Slit2 in repulsion and enhanced migration of trunk, but not vagal, neural crest cells. J Cell Biol. 2003; 162(2):269-79. PMC: 2172792. DOI: 10.1083/jcb.200301041. View

19.

Yntema C, HAMMOND W . The origin of intrinsic ganglia of trunk viscera from vagal neural crest in the chick embryo. J Comp Neurol. 1954; 101(2):515-41. DOI: 10.1002/cne.901010212. View

20.

Pomeranz H, Gershon M . Colonization of the avian hindgut by cells derived from the sacral neural crest. Dev Biol. 1990; 137(2):378-94. DOI: 10.1016/0012-1606(90)90262-h. View