Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • News & Views
  • Published:

Motility

Hirschsprung disease — laying down a suitable path

For many patients with Hirschsprung disease, the underlying pathogenic mechanisms are unknown. A new study using a novel line of transgenic mice and tissue from patients with Hirschsprung disease suggests that overproduction of collagen VI could contribute to pathogenesis and the increased incidence of Hirschsprung disease in patients with Down syndrome.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Over-production of collagen VI by ENCCs retards their migration.

References

  1. McKeown, S. J., Stamp, L., Hao, M. M. & Young, H. M. Hirschsprung disease: a developmental disorder of the enteric nervous system. Wiley Interdiscip. Rev. Dev. Biol. 2, 113–129 (2013).

    Article  CAS  Google Scholar 

  2. Alves, M. M. et al. Contribution of rare and common variants determine complex diseases — Hirschsprung disease as a model. Dev. Biol. 382, 320–329 (2013).

    Article  CAS  Google Scholar 

  3. Obermayr, F., Hotta, R., Enomoto, H. & Young, H. M. Development and developmental disorders of the enteric nervous system. Nat. Rev. Gastroenterol. Hepatol. 10, 43–57 (2013).

    Article  CAS  Google Scholar 

  4. Avetisyan, M., Schill, E. M. & Heuckeroth, R. O. Building a second brain in the bowel. J. Clin. Invest. 125, 899–907 (2015).

    Article  Google Scholar 

  5. Newgreen, D. F., Dufour, S., Howard, M. J. & Landman, K. A. Simple rules for a 'simple' nervous system? Molecular and biomathematical approaches to enteric nervous system formation and malformation. Dev. Biol. 382, 305–319 (2013).

    Article  CAS  Google Scholar 

  6. Breau, M. A., Dahmani, A., Broders-Bondon, F., Thiery, J. P. & Dufour, S. β1 integrins are required for the invasion of the caecum and proximal hindgut by enteric neural crest cells. Development 136, 2791–2801 (2009).

    Article  CAS  Google Scholar 

  7. Soret, R. et al. A collagen VI-dependent pathogenic mechanism for Hirschsprung's disease. J. Clin. Invest. 125, 4483–4496 (2015).

    Article  Google Scholar 

  8. Bergeron, K. F. et al. Male-biased aganglionic megacolon in the TashT mouse line due to perturbation of silencer elements in a large gene desert of chromosome 10. PLoS Genet. 11, e1005093 (2015).

    Article  Google Scholar 

  9. Akbareian, S. E. et al. Enteric neural crest-derived cells promote their migration by modifying their microenvironment through tenascin-C production. Dev. Biol. 382, 446–456 (2013).

    Article  CAS  Google Scholar 

  10. Emison, E. S. et al. A common sex-dependent mutation in a RET enhancer underlies Hirschsprung disease risk. Nature 434, 857–863 (2005).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

H.M.Y. is supported by National Health and Medical Research Council (NHMRC) Senior Research Fellowship APP1002506; S.J.M. is supported by NHMRC project grants APP1047953 and APP1043397.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Heather M. Young.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Young, H., McKeown, S. Hirschsprung disease — laying down a suitable path. Nat Rev Gastroenterol Hepatol 13, 7–8 (2016). https://doi.org/10.1038/nrgastro.2015.213

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrgastro.2015.213

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing