Modeling Development and Disease in Our “Second” Brain

  • Kerry A. Landman
  • Benjamin J. Binder
  • Donald F. Newgreen
Conference paper
Part of the Lecture Notes in Computer Science book series (LNCS, volume 7495)


The enteric nervous system (ENS) in our gastrointestinal tract, nicknamed the “second brain”, is responsible for normal gut function and peristaltic contraction. Embryonic development of the ENS involves the colonization of the gut wall from one end to the other by a population of proliferating neural crest (NC) cells. Failure of these cells to invade the whole gut results in the relatively common, potentially fatal condition known as Hirschsprung disease (HSCR). Cellular automata models provide insight into the colonization process at both the individual cell-level and population-level. Our models generated experimentally testable predictions, which have subsequently been confirmed. The model results imply that HSCR is chiefly a NC cell proliferation defect and not, as previously thought, a NC cell motility defect. These results have important implications for HSCR; namely stochastic effects can determine success or failure of the colonization process for a certain range of NC cell proliferation rates.


Cellular Automata Motility Proliferation Frontal Expansion Stochastic Hirschsprung disease 


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  1. 1.
    Gershon, M.D.: The second brain: A groundbreaking new understanding of nervous disorders of the stomach and intestine. HarperCollins, New York (1998)Google Scholar
  2. 2.
    Heanue, T.A., Pachnis, V.: Enteric nervous system development and Hirschsprungs disease: advances in genetic and stem cell studies. Nat. Rev. Neurosci. 8, 466–479 (2007)CrossRefGoogle Scholar
  3. 3.
    Zhang, D., Brinas, I.M., Binder, B.J., Landman, K.A., Newgreen, D.F.: Neural crest regionalisation for enteric nervous system formation: Implications for Hirschsprungs Disease and stem cell therapy. Dev. Biol. 339, 280–294 (2010)CrossRefGoogle Scholar
  4. 4.
    Binder, B.J., Landman, K.A., Simpson, M.J., Mariani, M., Newgreen, D.F.: Modeling proliferative tissue growth: A general approach and an avian case study. Phys. Rev. E 78, 031912 (2008)Google Scholar
  5. 5.
    Young, H.M., Bergner, A.J., Anderson, R.B., Enomoto, H., Milbrandt, J., Newgreen, D.F., Whitington, P.M.: Dynamics of neural crest-derived cell migration in the embryonic mouse gut. Dev. Biol. 270, 455–473 (2004)CrossRefGoogle Scholar
  6. 6.
    Simpson, M.J., Zhang, D.C., Mariani, M., Landman, K.A., Newgreen, D.F.: Cell proliferation drives neural crest cell invasion of the intestine. Dev. Biol. 302, 553–568 (2007)CrossRefGoogle Scholar
  7. 7.
    Chowdhury, D., Schadschneider, A., Nishinari, K.: Physics of transport and traffic phenomena in biology: from molecular motors and cells to organisms. Phys. Life Rev. 2, 318–352 (2005)CrossRefGoogle Scholar
  8. 8.
    Burns, A.J., Delalande, J.M., Le Douarin, N.M.: In ovo transplantation of enteric nervous system precursors from vagal to sacral neural crest results in extensive hindgut colonisation. Dev. 129, 2785–2796 (2002)Google Scholar
  9. 9.
    Murray, J.D., Mathematical Biology, I.: An Introduction, 3rd edn. Springer, Heidelberg (2002)MATHGoogle Scholar
  10. 10.
    Hao, M.M., Anderson, R.B., Young, H.M.: Development of enteric neuron diversity. J. Cell. Mol. Med. 13, 1193–1210 (2009)CrossRefGoogle Scholar
  11. 11.
    Landman, K.A., Fernando, A.E., Zhang, D., Newgreen, D.F.: Building stable chains with motile agents: Insights into the morphology of enteric neural crest cell migration. J. Theor. Biol. 276, 250–268 (2011)CrossRefGoogle Scholar
  12. 12.
    Simpson, M.J., Landman, K.A., Hughes, B.D., Newgreen, D.F.: Looking inside an invasion wave of cells using continuum models: Proliferation is the key. J. Theor. Biol. 243, 343–360 (2006)MathSciNetCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Kerry A. Landman
    • 1
  • Benjamin J. Binder
    • 2
  • Donald F. Newgreen
    • 3
  1. 1.Department of Mathematics and StatisticsUniversity of MelbourneAustralia
  2. 2.School of Mathematical SciencesUniversity of AdelaideAustralia
  3. 3.Murdoch Childrens Research InstituteRoyal Children’s HospitalParkvilleAustralia

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