Position-Dependent Growth Control and Pattern Formation in Limb Regeneration

  • Susan V. Bryant
  • David M. Gardiner
Part of the NATO ASI Series book series (NSSA, volume 172)


Results from experimental studies in regenerating and developing amphibian limbs have led us to conclude that growth and pattern formation are coordinately controlled (French et al., 1976; Bryant et al., 1981; Bryant et al., 1987). This conclusion is based on two propositions: (1) cells possess information about their position in the limb (i.e. cells have positional values); and (2) whenever discontinuities exist in the array of positional values, interactions between adjacent cells with different positional values will result in the stimulation of growth and in the intercalation of appropriate intervening positional values. Consequently, growth will cease when all positional disparities have been resolved. As we discuss below, cellular interactions resulting in the stimulation of growth can occur during normal development as a result of cell rearrangements within the limb field, during regeneration as a result of cell migration associated with wound healing, or in experimental situations as a result of grafting to bring cells with disparate positional properties (e.g. anterior and posterior) into contact. Hence, this view can account for the initiation, maintenance and termination of limb growth and patterning during normal development, after amputation, as well as after a variety of experimental manipulations.


Positional Information Limb Development Limb Cell Ambystoma Mexicanum Limb Outgrowth 
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  1. Aono, H., and Ide, H., 1988, A gradient of responsiveness to the growth-promoting activity of ZPA (Zone of polarizing activity in the chick limb bud), Devel. Biol., 128:136–141.CrossRefGoogle Scholar
  2. Borgens, R.B., 1984, Are limb development and limb regeneration both initiated by an integumentary wounding? A hypothesis., Differentiation, 28:87–93.PubMedCrossRefGoogle Scholar
  3. Borgens, R.B., Callahan, L. and Rouleau, M.F., 1987, Anatomy of axolotl flank integument during limb bud development with special reference to a transcutaneous current predicting limb formation, J. Exp. Zool., 244:203–214.PubMedCrossRefGoogle Scholar
  4. Borgens, R.B., Rouleau, M.F. and DeLanney, L.E., 1983, A steady efflux of ionic current predicts hind limb development in the axolotl, J. Exp. Zoll., 228:491–503.CrossRefGoogle Scholar
  5. Bryant, P.J. and Simpson, P., 1984, Intrinsic and extrinsic control of growth in developing organs, Quart. Rev. Biol. 59:387–415.PubMedCrossRefGoogle Scholar
  6. Bryant, S.V., 1976, Regenerative failure of double half limbs in Notophthalmus viridescens. Nature, 263:676–679.PubMedCrossRefGoogle Scholar
  7. Bryant, S.V. and Baca, B., 1978, Regenerative ability of double-half and half upper arms in the newt, Notophthalmus viridescens, J. Exp. Zool., 204:307–324.CrossRefGoogle Scholar
  8. Bryant, S., French, V. and Bryant, P., 1981, Distal regeneration and symmetry, Science, 212:993–1002.PubMedCrossRefGoogle Scholar
  9. Bryant, S.V., Gardiner, D.M. and Muneoka, K., 1987, Limb development and regeneration, Amer. Zool., 27:675–696.Google Scholar
  10. Bryant, S.V., Holder, N. and Tank, P., 1982, Cell-cell interactions and distal outgrowth in amphibian limbs, Amer. Zool., 22:143–151.Google Scholar
  11. Carlson, B.M., 1975a, Multiple regeneration from axolotl limb stumps bearing cross-transplanted minced muscle regenerates, Devel. Biol., 45:203–208.CrossRefGoogle Scholar
  12. Carlson, B.M., 1975b, The effects of rotation and positional change of stump tissues upon morphogenesis of the regenerating axolotl limb, Devel. Biol., 47:269–291.CrossRefGoogle Scholar
  13. Chevallier, A., Kieny, M. and Mauger, A., 1977, Limb-somite relationship: Origin of the limb musculature, J. Embryol. exp. Morph., 41:245–258.PubMedGoogle Scholar
  14. Dunis, D.A. and Namenwirth, M., 1977, The role of grafted skin in the regeneration of X-irradiated axolotl limbs, Devel. Biol., 56:97–109.CrossRefGoogle Scholar
  15. Egar, M.W., 1988, Accessory limb production by nerve-induced cell proliferation, Anat. Rec., 221:550–564.PubMedCrossRefGoogle Scholar
  16. Fallon, J.F. and Crosby, G.M., 1977, Polarising zone activity in limb buds of amniotes. in: “Vertebrate Limb and Somite Morphogenesis”, D.A. Ede, J.R. Hinchliffe and M. Balls, eds., Cambridge University Press, Cambridge.Google Scholar
  17. French, V., Bryant, P.J. and Bryant, S.V., 1976, Pattern regulation in epimorphic fields, Science, 193:969–981.PubMedCrossRefGoogle Scholar
  18. Gardiner, D.M., Muneoka, K. and Bryant, S.V., 1986, The migration of dermal cells during blastema formation in axolotls, Devel. Biol., 118:488–493.CrossRefGoogle Scholar
  19. Gardiner, D.M. and Bryant, S.V., 1988, The organization of positional information within the urodele limb (in preparation).Google Scholar
  20. Goss, R.J., 1956, The relation of bone to the histogenesis of cartilage in regenerating forelimbs and tails of adult Triturus viridescens, J. Morph., 98:89–123.CrossRefGoogle Scholar
  21. Hanken, J., 1986, Developmental evidence for amphibian origins, Evol. Biol., 20:389–417.CrossRefGoogle Scholar
  22. Holder, N. and Tank, P.W., 1979, Morphogenetic interactions occurring between blastemas and stumps after exchanging blastemas between normal and double-half forelimbs in the axolotl, Ambystoma mexicanum, Devel. Biol., 68:271–279.CrossRefGoogle Scholar
  23. Kelley, R.O. and Bluemink, J.G., 1974, An ultrastructural analysis of cell and matrix differentiation during early limb development in Xenopus laevis, Devel. Biol., 37:1–17.CrossRefGoogle Scholar
  24. Kelly, D.J. and Tassava, R.A., 1973, Cell division and ribonucleic acid synthesis during the initiation of limb regeneration in larval axolotls (Ambystoma mexicanum), J. Exp. Zool., 185:45–54.PubMedCrossRefGoogle Scholar
  25. Lheureux, E., 1975, Nouvelles donnees sur les rôles de la peau et des tissus internes dans la regeneration du membre du triton Pleurodeles waltlii Michah (Amphibien Urodele), Wilhelm Roux’s Arch., 176:285–301.CrossRefGoogle Scholar
  26. Lheureux, E., 1983, The origin of tissues in the x-irradiated regenerating limb of the newt Pleurodeles waltlii, in: “Limb Development and Regeneration, Part A”, J.F. Fallon and A.I. Caplan, eds., Alan R. Liss, Inc., New York.Google Scholar
  27. Maden, M., 1978, Neurotrophic control of the cell cycle during amphibian limb regeneration, J. Embryol. exp. Morph., 48:169–175.PubMedGoogle Scholar
  28. Maden, M. and Holder, N., 1984, Axial characteristics of nerve induced supernumerary limbs in the axolotl, Roux’s Arch. Dev. Biol., 193:394–401.Google Scholar
  29. Martin, P. and Lewis, J., 1986, Normal development of the skeleton in chick limb buds devoid of dorsal ectoderm, Devel. Biol., 118:233–246.CrossRefGoogle Scholar
  30. Muneoka, K. and Bryant, S.V., 1984, Cellular contribution to supernumerary limbs in the axolotl, Ambystoma mexicanum, Devel. Biol., 105:166–178.CrossRefGoogle Scholar
  31. Muneoka, K., and Murad, E.H.B., 1987, Intercalation and the cellular origin of supernumerary limbs in Xenopus, Development, 99:521–526.PubMedGoogle Scholar
  32. Muneoka, K., Fox, W. and Bryant, S.V., 1986, Cellular contribution from dermis and cartilage to the regenerating limb blastema in axolotls, Devel. Biol., 116:256–260.CrossRefGoogle Scholar
  33. Muneoka, K., Holler-Dinsmore, G.V. and Bryant, S.V., 1985, A quantitative analysis of regeneration from chimaeric limb stumps in the axolotl, J. Embryol. exp. Morph., 90:1–12.PubMedGoogle Scholar
  34. Muneoka, K., Holler-Dinsmore, G. and Bryant, S.V., 1986, Pattern discontinuity, polarity and directional intercalation in axolotl limbs, J. Embryol. exp. Morph., 93:51–72.PubMedGoogle Scholar
  35. Newman, S.A., Pautou, M.-P. and Kieny, M., 1981, The distal boundary of myogenic primordia in chimeric avian limb buds and its relation to an accessible population of cartilage progenitor cells, Devel. Biol., 84:440–448.CrossRefGoogle Scholar
  36. Noden, D.M., 1986, Patterning of avian craniofacial muscles, Devel. Biol., 116:347–356.CrossRefGoogle Scholar
  37. Robinson, K.R., 1983, Endogenous electrical current leaves the limb and prelimb region of the Xenopus embryo, Devel. Biol., 97:203–211.CrossRefGoogle Scholar
  38. Rollman-Dinsmore, C. and Bryant, S.V., 1982, Pattern regulation between hind- and forelimbs after blastema exchanges and skin grafts in Notophthalmus viridescens, J. Exp. Zool., 223:51–56.PubMedCrossRefGoogle Scholar
  39. Rubin, L. and Saunders, J.W., Jr., 1972, Ectodermal-mesodermal interactions in the growth of limb buds in the chick embryo: Constancy and temporal limits of the ectodermal induction, Devel. Biol., 28:94–112.CrossRefGoogle Scholar
  40. Saunders, J.W., Jr., 1948, The proximo-distal sequence of origin of the parts of the chick wing and the role of ectoderm. J. Exp. Zool., 108:363–403.PubMedCrossRefGoogle Scholar
  41. Saunders, J.W., Jr. and Reuss, C., 1974, Inductive and axial properties of prospective wing-bud mesoderm in the chick embryo, Devel. Biol., 38:41–50.CrossRefGoogle Scholar
  42. Sessions, S.K. and Bryant, S.V., 1988, Regenerative ability is an intrinsic property of limb cells in Xenopus, J. Exp. Zool., (in press).Google Scholar
  43. Sessions, S.K., Gardiner, D.M. and Bryant, S.V., 1989, Compatible limb patterning mechanisms in urodeles and anurans, Devel. Biol., (in press).Google Scholar
  44. Shubin, N.H. and Alberch, P., 1986, A morphogenetic approach to the origin and basic organization of the tetrapod limb, Evol. Biol., 20:319–387.CrossRefGoogle Scholar
  45. Slack, J.M.W., 1980, Morphogenetic properties of the skin in axolotl limb regeneration, J. Embryol. exp. Morph., 58:265–288.PubMedGoogle Scholar
  46. Stock, G.B. and Bryant, S.V., 1981, Studies of digit regeneration and their implications for theories of development and evolution of vertebrate limbs, J. Exp. Zool., 216:423–433.PubMedCrossRefGoogle Scholar
  47. Stocum, D.L., 1978, Regeneration of symmetrical hindlimbs in larval salamanders, Science, 200:790–793.PubMedCrossRefGoogle Scholar
  48. Stocum, D.L., 1980, Intercalary regeneration of symmetrical thighs in the axolotl, Ambystoma mexicanum, Devel. Biol. 79:276–295.CrossRefGoogle Scholar
  49. Stocum, D.L., 1981, Distal transformation in regenerating double anterior axolotl limbs, J. Embryol. exp. Morph., 65 (supplement): 3–18.Google Scholar
  50. Stocuiti, D.L. and Dearlove, G.E., 1972, Epidermal-mesodermal interaction during morphogenesis of the limb regeneration blastema in larval salamanders, J. Exp. Zool.. 181:49–62.CrossRefGoogle Scholar
  51. Tank, P.W., 1978, The failure of double-half forelimbs to undergo distal transformation following amputation in the axolotl, Ambystoma mexicanum, J. Exp. Zool., 204:325–336.CrossRefGoogle Scholar
  52. Tank, P.W., 1979, Positional information in the forelimb of the axolotl: Experiments with double-half tissues, Devel. Biol., 73:11–24.CrossRefGoogle Scholar
  53. Tank, P.W., 1981, The ability of localized implants of whole or minced dermis to disrupt pattern formation in the regenerating forelimb of the axolotl, Amer. J. Anat., 162:315–326.PubMedCrossRefGoogle Scholar
  54. Tank, P.W., 1987, The effect of nonlimb tissues on forelimb regeneration in the axolotl, Ambystoma mexicanum, J. Exp. Zool., 244:409–423.CrossRefGoogle Scholar
  55. Tank, P.W. and Holder, N., 1978, The effect of healing time on the proximo-distal organization of double-half forelimb regenerates in the axolotl, Ambystoma mexicanum, Devel. Biol.. 66:72–85.CrossRefGoogle Scholar
  56. Tank, P.W. and Holder, N., 1981, Pattern regulation in the regenerating limbs of urodele amphibians, Quart. Rev. Biol., 56:113–142.CrossRefGoogle Scholar
  57. Tassava, R.A., Bennett, L.L. and Zitnik, G.D., 1974, DNA synthesis without mitosis in amputated denervated forelimbs of larval axolotls. J. Exp. Zool., 190:111–116.PubMedCrossRefGoogle Scholar
  58. Twitty, V.C. and Schwind, J.L., 1931, The growth of eyes and limbs transplanted heteroplastically between two species of Amblystoma, J. Exp. Zool., 59:61–86.CrossRefGoogle Scholar
  59. Westoll, T., 1943, The origin of the primitive tetrapod limb, Proc. R. Soc. Lond. B, 131:373–393.CrossRefGoogle Scholar
  60. Wigmore, P., 1986, Regeneration from half lower arms in the axolotl, J. Embryol. exp. Morph., 95:247–260.PubMedGoogle Scholar
  61. Wigmore, P. and Holder, N., 1985, Regeneration from isolated half limbs in the upper arm of the axolotl, J. Embryol. exp. Morph., 89:333–347.PubMedGoogle Scholar
  62. Wigmore, P. and Holder, N., 1986, The effect of replacing different regions of limb skin with head skin on regeneration in the axolotl, J. Embryol. exp. Morph., 98:237–249.PubMedGoogle Scholar
  63. Wolpert, L., 1969, Positional information and the spatial pattern of cellular differentiation, J. Theoret. Biol., 25:1–47.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • Susan V. Bryant
    • 1
  • David M. Gardiner
    • 1
  1. 1.Developmental Biology CenterUniversity of California, IrvineIrvineUSA

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