Abstract
A defining characteristic of the enteric nervous system (ENS) is mesoscale patterned entities called ganglia. Ganglia are clusters of neurons with associated enteric neural crest (ENC) cells, which form in the simultaneously growing gut wall. At first, the precursor ENC cells proliferate and gradually differentiate to produce the enteric neurons; these neurons form clusters with ENC scattered around and later lying on the periphery of neuronal clusters. By immunolabelling neural cell–cell adhesion molecules, the adhesive capacity of neurons is determined to be greater than that of ENC cells. Using a probabilistic cellular automata (PCA) model, we test the hypothesis that local rules governing differential adhesion of neuronal agents and ENC agents will produce clusters that emulate ganglia. The clusters are relatively stable, relatively uniform and small in size, of fairly uniform spacing, with a balance between the number of neuronal and ENC agents. These features are attained in both fixed and growing domains, reproducing, respectively, organotypic in vitro and in vivo observations. Various threshold criteria governing ENC agent proliferation and differentiation and neuronal agent inhibition of differentiation are important for sustaining these characteristics. This investigation suggests possible explanations for observations in normal and abnormal ENS development.
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Binder, B.J., Landman, K.A.: Exclusion processes on a growing domain. J. Theor. Biol. 259, 541–551 (2009)
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)
Breau, M.A., Pietri, T., Eder, O., Blanche, M., Brakebusch, C., Fassler, R., Thiery, J.P., Dufour, S.: Lack of \(\beta \)1 integrins in enteric neural crest cells leads to a Hirschsprung-like phenotype. Development 33, 1725–1734 (2006)
Chalazonitis, A., Gershon, M.D., Green, L.A.: Cell death and the develo** enteric nervous system. Neurochem. Int. 61, 839–847 (2012)
Daub, J.T., Merks, R.M.H.: A cell-based model of extracellular-matrix-guided endothelial cell migration during angiogenesis. Bull. Math. Biol. 75, 1377–1399 (2013)
Foty, R.A., Steinberg, M.S.: Cadherin-mediated cell-cell adhesion and tissue segregation in relation to malignancy. Int. J. Dev. Biol. 48, 397–409 (2004)
Foty, R.A., Steinberg, M.S.: The differential adhesion hypothesis: a direct evaluation. Dev. Biol. 278, 255–263 (2005)
Glazier, J.A., Graner, F.: Simulation of the differential adhesion driven rearrangement of biological cells. Phys. Rev. E 47, 2128–2154 (1993)
Graner, F., Glazier, J.A.: Simulation of biological cell sorting using a two-dimensional extended Potts model. Phys. Rev. Lett. 69, 2013–2016 (1992)
Hackett-Jones, E.J., Landman, K.A., Newgreen, D.F., Zhang, D.: On the role of differential adhesion in gangliogenesis in the enteric nervous system. J. Theor. Biol. 287, 148–159 (2011)
Hao, M.M., Anderson, R.B., Kobayashi, K., Whitington, P.M., Young, H.M.: The migratory behaviour of immature enteric neurons. Dev. Neurobiol. 69, 22–35 (2009)
Hao, M.M., Anderson, R.B., Young, H.M.: Development of enteric neuron diversity. J. Cell. Mol. Med. 13, 1193–1210 (2009)
Hearn, C.J., Young, H.M., Ciampoli, D., Lomax, A.E., Newgreen, D.F.: Catenary cultures of embryonic gastrointestinal tract support organ morphogenesis, motility, neural crest cell migration, and cell differentiation. Dev. Dyn. 214, 239–247 (1999)
Hendershot, T.J., Liu, H., Sarkar, A.A., Giovannucci, D.R., Clouthier, D.E., Abe, M., Howard, M.J.: Expression of Hand2 is sufficient for neurogenesis and cell type-specific gene expression in the enteric nervous system. Dev. Dyn. 236, 93–105 (2007)
Horton, J.D.: A polynomial-time algorithm to find a shortest cycle basis of a graph. SIAM J. Comput. 16, 359–366 (1987)
Hoshen, J., Kopelman, R.: Percolation and cluster distribution. I. Cluster multiple labeling technique and critical density algorithm. Phys. Rev. B 14, 3438–3445 (1976)
Hotta, R., Anderson, R.B., Kobayashi, K., Newgreen, D.F., Young, H.M.: Effects of tissue age, presence of neurones and endothelin-3 on the ability of enteric neurone precursors to colonize recipient gut: implications for cell-based therapies. Neurogastroenterol. Motil. 22, 331–e86 (2010)
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)
Landman, K.A., Binder, B.J., Newgreen, D.F.: Modeling development and disease in our “second” brain. Lect. Notes Comput. Sci. 7495, 405 (2012)
Longo, D., Peirce, S.M., Skalak, T.C., Davidson, L., Marsden, M., Dzamba, B., DeSimone, D.W.: Multicellular computer simulation of morphogenisis: blastocoel roof thinning and matrix assembly in Xenopus laevis. Dev. Biol. 271, 210–222 (2004)
Mehlhorn, K., Michail, D.: Implementing minimum cycle basis algorithms. J. Exp. Algorithmics 11, 1–14 (2006)
Meier-Ruge, W.A., Bruder, E., Kapur, R.P.: Intestinal neuronal dysplasia type B: one giant ganglion is not good enough. Pediatr. Dev. Pathol. 9, 444–452 (2006)
Merks, R.M.H., Glazier, J.A.: A cell-centered approach to developmental biology. Physica A 352, 113–130 (2005)
Newgreen, D.F., Southwell, B., Hartley, L., Allan, I.J.: Migration of enteric neural crest cells in relation to growth of the gut in avian embryos. Acta Anat. 157, 105–115 (1996)
Newgreen, D., Young, H.M.: Enteric nervous system: development and developmental disturbances-part 1. Pediatr. Dev. Pathol. 5, 224–247 (2002)
Peirce, S.M., Van Gieson, E.J., Skalak, T.C.: Multicellular simulation predicts microvascular patterning and in silico tissue assembly. FASEB J. 18(6), 731–733 (2004). https://doi.org/10.1096/fj.03-0933fje
Savill, N.J., Sherratt, J.A.: Control of epidermal stem cell clusters by notch-mediated lateral induction. Dev. Biol. 258, 141–153 (2003)
Simpson, M.J., Merrifield, A., Landman, K.A., Hughes, B.D.: Simulating invasion with cellular automata. Phys. Rev. E 76, 021918 (2007)
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)
Steinberg, M.S.: Mechanism of tissue reconstruction by dissociated cells.II. Time course of events. Science 137, 762–763 (1962)
Steinberg, M.S.: On the mechanism of tissue reconstruction by dissociated cells, III. Free energy relations and the reorganisation of fused, heteronomic tissue fragments. Proc. Natl. Acad. Sci. USA 48, 1769–1776 (1962)
Steinberg, M.S.: On the mechanism of tissue reconstruction by dissociated cells, I. population kinetics, differential adhesiveness, and the absence of directed migration. Proc. Natl. Acad. Sci. USA 48, 1577–1582 (1962)
Sulsky, D.: A model of cell sorting. J. Theor. Biol. 106, 275–301 (1984)
Townes, P.L., Holtfreter, J.: Directed movements and selective adhesion of embryonic amphibian cells. J. Exp. Zool. 128, 53–120 (1955)
Wedel, T., Roblick, U.J., Ott, V., Eggers, R., Schiedeck, T.H.K., Krammer, H.J., Bruch, H.P.: Oligoneuronal hypoganglionosis in patients with idiopathic slow-transit constipation. Dis. Colon Rectum 45, 54–62 (2002)
Wilson, H.V.: On some phenomena of coalescence and regeneration in sponges. J. Exp. Zool. 5, 245–258 (1907)
Yin, M., King, S.K., Hutson, J.M., Chow, C.W.: Multiple endocrine neoplasia type 2B diagnosed on suction rectal biopsy in infancy: a report of 2 cases. Pediatr. Dev. Pathol. 9, 56–60 (2006)
Young, H.M., Bergner, A.J., Muller, T.: Acquisition of neuronal and glial markers by neural crest-derived cells in the mouse intestine. J. Comp. Neurol. 456, 1–11 (2003)
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)
Young, H.M., Turner, K.N., Bergner, A.J.: The location and phenotype of proliferating neural-crest-derived cells in the develo** mouse gut. Cell Tissue Res. 320, 1–9 (2005)
Zhang, D., Brinas, I.M., Binder, B.J., Landman, K.A., Newgreen, D.F.: Neural crest regionalisation for enteric nervous system formation: implications for Hirschsprung’s Disease and stem cell therapy. Dev. Biol. 339, 280–294 (2010)
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This work was supported by Australian Research Council and National Health and Medical Research Council grants. Thanks are given to Emily Hackett-Jones and Dongcheng Zhang. MCRI facilities are supported by the Victorian Government’s Operational Infrastructure Support Program.
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Landman, K.A., Newgreen, D.F. (2018). PCA Modelling of Multi-species Cell Clusters: Ganglion Development in the Gastrointestinal Nervous System. In: Louis, PY., Nardi, F. (eds) Probabilistic Cellular Automata. Emergence, Complexity and Computation, vol 27. Springer, Cham. https://doi.org/10.1007/978-3-319-65558-1_17
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