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

Authors

  • AM Goldstein,

    1. Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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  • RMW Hofstra,

    1. Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands
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  • AJ Burns

    Corresponding author
    1. Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands
    2. Neural Development and Gastroenterology Units, UCL Institute of Child Health, London, UK
    • Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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  • The authors have no conflict of interest.

Corresponding author: Alan J. Burns,

Neural Development and

Gastroenterology Units, UCL Institute of

Child Health, 30 Guilford Street,

London, WC1N 1EH, UK.

Tel.: +44 20 7905 2721;

fax: +44 20 7831 4366;

e-mail: alan.burns@ucl.ac.uk

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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