Cited by 183Congenital gastrointestinal and neural anomaliesGastrointestinal motility and disordersDevelopmental Biology and Gene Regulation

Building a brain in the gut: development of the enteric nervous system

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Goldstein, AM, Hofstra, RMW, Burns, AJ·2013·Clinical Genetics

Abstract

The enteric nervous system (ENS), the intrinsic innervation of the gastrointestinal tract, is an essential component of the gut neuromusculature and controls many aspects of gut function, including coordinated muscular peristalsis. The ENS is entirely derived from neural crest cells (NCC) which undergo a number of key processes, including extensive migration into and along the gut, proliferation, and differentiation into enteric neurons and glia, during embryogenesis and fetal life. These mechanisms are under the molecular control of numerous signaling pathways, transcription factors, neurotrophic factors and extracellular matrix components. Failure in these processes and consequent abnormal ENS development can result in so‐called enteric neuropathies, arguably the best characterized of which is the congenital disorder Hirschsprung disease (HSCR), or aganglionic megacolon. This review focuses on the molecular and genetic factors regulating ENS development from NCC, the clinical genetics of HSCR and its associated syndromes, and recent advances aimed at improving our understanding and treatment of enteric neuropathies.

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  • The ENS is similar to the brain regarding structure, function, and chemical coding, and has been described as "the second brain" or "the brain within the gut".

    “Since the ENS is similar to the brain regarding structure, function, and chemical coding, it has been described as “the second brain” or “the brain within the gut” (26).”

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  1. [10]Kalcheim C Le Douarin NM The Neural Crest 1999 Cambridge University Press Cambridge

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Authors
Goldstein, A., Hofstra, R., & Burns, A.
Affiliations
  • Harvard University (US)
  • Department of Clinical Genetics Erasmus Medical Center Rotterdam The Netherlands
  • Erasmus MC (NL)
Corresponding author
Burns, AJ
Venue
Clinical Genetics
Publisher
Wiley
Published
2013-04
Volume
83
Issue
4
Pages
307-316
ISSN
  • 0009-9163 (ISSN-L)
  • 1399-0004
OpenAlex
W1892969415
Cited by
183
References
111
Citations by year
2026: 4 · 2025: 14 · 2024: 10 · 2023: 13 · 2022: 16 · 2021: 7 · 2020: 11 · 2019: 12 · 2018: 15 · 2017: 20 · 2016: 23 · 2015: 19 · 2014: 6 · 2013: 12 · 2012: 1
FWCI
2.27
Type
journal article
Language
en
Open access
Locations
  • Clinical Genetics (publishedVersion)
  • PubMed (publishedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Funders
  • National Institutes of Health
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK080914)
Topics
  • Health Sciences › Medicine › Surgery › Congenital gastrointestinal and neural anomalies
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
enteric nervous system development, neural crest cells, enteric neurons, enteric glial cells, Hirschsprung disease, enteric neuropathy, intestinal motility, peristalsis, signaling pathways, transcription factors, neurotrophic factors, extracellular matrix, congenital disorders
MeSH terms
Animals, Brain, Humans, Neurons, Signal Transduction, Enteric Nervous System, Gastrointestinal Tract

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