Abstract
Neurulation, the curling of the neuroepithelium to form the neural tube, is an essential component of the development of animal embryos. Defects of neural tube formation, which occur with an overall frequency of one in 500 human births, are the cause of severe and distressing congenital abnormalities. However, despite the fact that there is increasing information from animal experiments about the mechanisms which effect neural tube formation, much less is known about the fundamental causes of neural tube defects (NTD). The use of computer models provides one way of gaining clues about the ways in which neurulation may be compromised. Here we employ one computer model to examine the robustness of different cellular mechanisms which are thought to contribute to neurulation. The model, modified from that of Odell et al (Odell, G.M., Oster, G., Alberch, P. and Burnside, B., (1981)) mimics neurulation by laterally propagating a wave of apical contraction along an active zone within a ring of cells. We link the results to experimental evidence gained from studies of embryos in which neurulation has been perturbed. The results indicate that alteration of one of the properties of non-neural tissue can delay or inhibit neurulation, supporting the idea, gained from observation of embryos bearing genes which predispose to NTD, that the tissue underlying the neuroepithelium may contribute to the elevation of the neural folds. The results also show that reduction of the contractile properties of a small proportion of the neuroepithelial cell population may have a profound effect on overall tissue profiling. The results suggest that the elevation of the neural folds, and hence successful neurulation, may be vulnerable to relatively minor deficiencies in cell properties.
Similar content being viewed by others
References
Althouse, R. and Ward, N. (1980). Survival and handicap of infants with spina bifida. Arch. Diseases Childhood 55: 845–850.
Beloussov, L.V., Dorfman, J.G. and Cherdantzev, V.G. (1975). Mechanical stresses and morphological patterns in amphibian embryos. J. Embryol. exp. Morph. 34: 559–574.
Bernfield, M., Banerjee, S., Koda, J. and Rapraeger, A. (1984). In: R.L. Trelsted, ed., The role of the extracelluar matrix in development. New York: Liss.
Carter, C.O. (1974). Genetics of common disorders. Dev. Med. Child Neurol. 16: 3–15.
Copp, A.J. and Bernfield, M. (1988a). Gylcosaminoglycans vary in accumulation along the neuraxis during spinal neurulation in the mouse embryo. Develop. Biol. 130: 573–582.
Copp, A.J. and Bernfield, M. (1988b). Accumulation of basement membrane-associated hyaluronate is reduced in the posterior neuropore region of mutant (curly tail) mouse embryos developing spinal neural tube defects. Develop. Biol. 130: 583–590.
Copp, S.N. and Wilson, D.B. (1981). Cranial glycosaminoglycans in early embryos of the loop-tail (Lp) mutant mouse. J. Craniofacial Genet. Dev. Biol. 1: 253–260.
Freeman, B.G. (1972). Surface modifications of neural epithelial cells during formation of the neural tube in rat embryo. J. Embryol. exp. Morph. 28: 437–448.
Garnham, E.A., Beck, F., Clarke, C.A. and Stanisstreet, M. (1983). Effects of glucose on rat embryos in culture. Diabetologia 25: 291–295.
Geelen, J.A.G. and Langman, J. (1977). Closure of the neural tube in the cephalic region of the mouse embryo. Anat. Rec. 189: 625–640.
Gordon, R. (1985). A review of the theories of vertebrate neurulation and their relationship to the mechanisms of neural tube birth defects. J. Embryol. exp. Morph. 89 (suppl.): 229–255.
Hanaway, J. and Welch, G. (1970). Anencephaly: a review and interpretation in terms of modern experimental embryology. Dis. Nerv. Sys. 31: 527–533.
His, W. (1874). Unsere Körperform und das physiologische Problem ihrer Enstehung, Briefe an einen befreundeten Naturforscher. Leipzig: F.C.W. Vogel.
Jacobson, A.G. and Gordon, R. (1976). Changes in the shape of the developing vertebrate nervous system analyzed experimentally, mathematically and by computer simulation. J. exp. Zool. 197: 191–246.
Jacobson, A.G. and Tam, P.P.L. (1982). Cephalic neurulation in the mouse embryo analyzed by SEM and morphometry. Anat. Rec. 203: 375–396.
Karfunkel, P. (1974). The mechanisms of neural tube formation. Int. Rev. Cytol. 38: 245–272.
Kaufman, M. (1979). Cephalic neurulation and optic vesicle formation in the early mouse embryo. Am. J. Anat. 155: 425–444.
Lee, H.Y., Koscuick, M.C., Nagele, R.G. and Roisen, F.J. (1983). Studies on the mechanism of neurulation in the chick: possible involvement of myosin in elevation of neural folds. J. Exp. Zool. 225: 449–457.
Lemire, R.J., Loeser, J.D., Leech, R.W. and Alvord, E.C. (1975). Normal and abnormal development of the human nervous system. New York: Harper and Row.
Lewis, W.H. (1947). Mechanics of invagination. Anat. Rec. 97: 137–156.
Moore, D.C.P. and Stanisstreet, M. (1986). Calcium requirement for neural fold elevation in rat embryos. Cytobios 47: 167–177.
Moore, D.C.P. and Stanisstreet, M. (1988). Perturbation of in vitro development of rodent embryos by calcium antagonist Quin-2. Cytobios 55: 133–146.
Moore, D.C.P., Stanisstreet, M. and Clarke, C.A. (1989). Morphological and physiological effects of β-hydroxybutyrate on rat embryos grown in vitro at different stages. Teratology 40: 237–251.
Moore, C.D.P., Stanisstreet, M. and Evans, G.E. (1987). Morphometric analyses of changes in cell shape in the neuroepithelium of mammalian embryos. J. Anat. 155: 87–99.
Moran, D.J. and Rice, R.W. (1976). Action of papaverine and ionophore A23187 on neurulation. Nature 261: 497–499.
Morriss, G.M. and New, D.A.T. (1979). Effect of oxygen concentration on morphogenesis of cranial neural folds and neural crest in cultured rat embryos. J. Embryol. exp. Morph. 54: 17–35.
Morriss, G.M. and Solursh, M. (1978a). Regional differences in mesenchyme cell morphology and glycosaminoglycans in early neural-fold stage rat embryos. J. Embryol. exp. Morph. 46: 37–52.
Morriss, G.M. and Solursh, M. (1978b). The role of primary mesenchyme in normal and abnormal morphogenesis of mammalian neural folds. Zoon. 6: 33–38.
Morriss-Kay, G.M. (1981). Growth and development of pattern in the cranial neural epithelium of rat embryos during neurulation. J. Embryol. exp. Morph. 65 (suppl.): 225–241.
Morriss-Kay, G.M. (1983). The effect of cytochalasin-D on structure and function of microfilament bundles during cranial neural tube formation in cultured rat embryos. J. Physiol. 345: 52p.
Morriss-Kay, G.M. and Crutch, B. (1982). Culture of rat embryos with β-D-xyloside: evidence of a role for proteoglycans in neurulation. J. Anat. 134: 491–506.
Morriss-Kay, G.M. and Tuckett, F. (1985). The role of microfilaments in cranial neurulation in rat embryos: effects of short-term exposure to cytochalasin-D. J. Embryol. exp. Morph. 88: 33–348.
Nagele, R.G., Pietrolungo, J.F. Lee, H. and Roisen, F. (1981). Diazepam-induced neural tube closure defects in explanted early chick embryos. Teratology 23: 343–349.
Odell, G.M. Oster, G., Alberch, P. and Burnside, B. (1981). The mechanical basis of morphogenesis. I Epithelial folding and invagination. Develop. Biol. 85: 446–462.
O'Shea, K.S. (1981). The cytoskeleton in neurulation: role of cations. Prog. Anat. 1: 35–60.
Pederson, J.F and Pederson, L.M. (1981). Early fetal growth delay detected by ultrasound marks an increased risk of congenital malformation in diabetic pregnancy. Brit. Med. J. 283: 269–271.
Roux, W. (1885) Zur Orientierung ueber enige Probleme der embryonalen Entwicklung. Z. Biol. 21: 411–526.
Sadler, T.W., Burridge, K. and Yonker, J. (1986). A potential role for spectrin during neurulation, J. Embryol. exp. Morph. 94: 73–82.
Sadler, T.W., Lessard, J.L., Greenberg, D. and Coughlin, P. (1982). Action distribution patterns in the mouse neural tube during neurulation. Science 215: 172–174.
Schoenwolf, G.C. (1982). On the morphogenesis of the early rudiments of the developing central nervous system. Scanning Electron Microscopy 1: 289–308.
Schwartz, H. (1980). Two-dimensional shape-feature indices. Mikroscopie (Wien) 37 (suppl.): 64–67.
Shepard, T.H. and Greenaway, J.C. (1977). Teratogenicity of cytochalasin D in the mouse. Teratology 16: 131–136.
Smedley, M.J. and Stanisstreet, M. (1985). Calcium and neurulation in mammalian embryos. J. Embryol. exp. Morph. 89: 1–14.
Smedley, M.J. and Stanisstreet, M. (1986) Calcium and neurulation in mammalian embryos. II. Effects of cytoskeleton inhibitors and calcium antagonists on the neural folds of rat embryos. J. Embryol. exp. Morph. 93: 167–178.
Solursh, M. and Morriss, G.M. (1977). Glycosaminoglycan synthesis in rat embryos during the formation of the primary mesenchyme and neural folds. Develop. Biol. 57: 75–86.
Spiers, P.S. (1982). Does growth retardation predispose the fetus to congenital malformation? Lancet 1: 312–314.
Stanisstreet, M. (1982). Calcium and wound healing in Xenopus embryos. J. Embryol. exp. Morph. 67: 195–205.
Stanisstreet, M., Dunnett, D.A., Goodbody, A.M. and Kelly, G. (1988). Computer measurement and modelling of changes in cell shape during animal development. In: P.J. Lloyd, ed., Particle Size Analysis, John Wiley.
Stanisstreet, M., Smedley, M.J. and Moore, D.C.P. (1984). Calcium and neurulation in mammalian embryos. J. Embryol. exp. Morph. 82 (suppl.): 215.
Stanisstreet, M., Smedley, M.J. and Snow, R.M. (1985) Tension and wound healing in amphibian early embryos. Acta. Embryol. Morphol. Exper. n.s. 6: 177–191.
Stanisstreet, M., Wakely, J. and England, M.A. (1980) Scanning electron microscopy of wound healing in Xenopus and chicken embryos. J. Embryol. exp. Morph. 59: 341–353.
Wiley, M.J. (1980) The effect of cytochalasins on the ultrastructure of neurulating hamster embryos in vivo. Teratology 22: 59–69.
Wilson, D.B. and Finta, L.A. (1980). Fine structure of the lumbrosacral neural folds in the mouse embryo. J. Embryol. exp. Morph. 55 279–290.
Wilson, D.B. and Hendrickx, A.G. (1984). Fine structural aspects of the cranial neuroepithelium in the early embryos of the Rhesus monkey. J. Craniofacial. Genet. Dev. Biol. 4: 85–94.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Dunnett, D., Goodbody, A. & Stanisstreet, M. Computer modelling of neural tube defects. Acta Biotheor 39, 63–79 (1991). https://doi.org/10.1007/BF00046408
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00046408