Intracephalic Embryonic Transplants

A New Experimental Preparation for Developmental Neurobiology
  • Lawrence F. Kromer


The purpose of the present review is to explore the possible use of “intracephalic” embryonic neural transplants to neonatal and adult recipients as model systems for analyzing various aspects of CNS development. Transplants of embryonic brain tissue into the CNS milieu of immature or adult recipients provide a unique opportunity to analyze both the subsequent development of the embryonic CNS tissue and the interaction of its immature constituent cells with cellular elements and products present in the CNS environment and circulatory system of the host animal.


Purkinje Cell Granule Cell Dentate Gyrus Locus Coeruleus Choroid Plexus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    May, R. M., 1930, La greffe dans l’oeil de rat blanc adulte du tissu cerebral de rat nouveau-né, Arch. Anat. Microsc. 26: 443.Google Scholar
  2. 2.
    Greene, H. S. M., and Arnold H., 1945, The homologous and heterologous transplantation of brain and brain tumors, J. Neurosurg. 2:315.CrossRefGoogle Scholar
  3. 3.
    Chatagnon, P.-A., 1952, Recherches sur la differenciation du neurone dans la greffe bréphoplastique endoculaire chez le rat blanc, Arch. Biol. 63:199.Google Scholar
  4. 4.
    Olson, L., and Seiger, A., 1972, Brain tissue transplanted to the anterior chamber of the eye. 1. Fluorescence histochemistry of immature catecholamine and 5-hydroxytryptamine neurons reinnervating the rat iris, Z. Zellforsch Mikrosk, Anat. 135:175.CrossRefGoogle Scholar
  5. 5.
    Hoffer, B., Seiger, Ȧ., Ljungberg, T., and Olson, L. 1974, Electrophysiological and cytological studies of brain in the anterior chamber of the eye: Maturation of cerebellar cortex in oculo, Brain Res. 79:165.PubMedCrossRefGoogle Scholar
  6. 6.
    Hoffer, B., Olson, L., Seiger, A., and Bloom, F., 1975, Formation of a functional adrenergic input to intraocular cerebellar grafts: Ingrowth of inhibitory sympathetic fibers, J. Neurobiol. 6:565.PubMedCrossRefGoogle Scholar
  7. 7.
    Seiger, Ȧ., and Olson, L., 1975, Brain tissue transplanted to the anterior chamber of the eye. 3. Substitution of lacking central noradrenaline input by host iris sympathetic fibers in the isolated cerebral cortex developed in oculo, Cell Tissue Res. 159:325.PubMedCrossRefGoogle Scholar
  8. 8.
    Seiger, A., and Olson, L., 1977, Quantitation of fiber growth in transplanted central monoamine neurons, Cell Tissue Res. 179:285.PubMedCrossRefGoogle Scholar
  9. 9.
    Yellin, H., 1976, Survival and possible trophic function of neonatal spinal cord grafts in the anterior chamber of the eye, Exp. Neurol. 51:579.PubMedCrossRefGoogle Scholar
  10. 10.
    Woodward, D. J., Seiger, Ȧ., Olson, L., and Hoffer, B. J., 1977, Intrinsic and extrinsic determinants of dendritic development as revealed by Golgi studies of cerebellar and hippocampal transplants in oculo, Exp. Neurol. 57:984.PubMedCrossRefGoogle Scholar
  11. 11.
    Olson, L., Freedman, H., Seiger, Ȧ., and Hoffer, B., 1977, Electrophysiology and cytology of hippocampal formation transplants in the anterior chamber of the eye. I. Intrinsic organization, Brain Res. 119:87.PubMedCrossRefGoogle Scholar
  12. 12.
    Goldowitz, D., Seiger, Ȧ., and Olson, L., 1982, Anatomy of the isolated area dentata grown in the rat anterior eye chamber, J. Comp. Neurol. 208:382.PubMedCrossRefGoogle Scholar
  13. 13.
    Dunn, E., 1917, Primary and secondary findings in a series of attempts to transplant cerebral cortex in the albino rat, J. Comp. Neurol. 27:565.CrossRefGoogle Scholar
  14. 14.
    Le Gros Clark, W. E., 1940, Neuronal differentiation in implanted foetal cortical tissue, J. Neurol. Psychiatry 3:263.CrossRefGoogle Scholar
  15. 15.
    Das, G. D., 1974, Transplantation of embryonic neural tissue in the mammalian brain. I. Growth and differentiation of neuroblasts from various regions of the embryonic brain in the cerebellum of neonate rats, TIT J. Life Sci. 4:93.PubMedGoogle Scholar
  16. 16.
    Das, G. D., 1975, Differentiation of dendrites in the transplanted neuroblasts in the mammalian brain, Adv. Neurol. 12:181.PubMedGoogle Scholar
  17. 17.
    Lund, R. D., and Hauschka, S. D., 1976, Transplanted neural tissue develops connections with host rat brain, Science 193:582.PubMedCrossRefGoogle Scholar
  18. 18.
    Zimmer, J., 1978, Development of the hippocampus and fascia dentata: Morphological and histochemical aspects, Prog. Brain Res. 48:171.PubMedCrossRefGoogle Scholar
  19. 19.
    Jaeger, C. B., and Lund, R. D., 1979, Efferent fibers from transplanted cerebral cortex of rats, Brain Res. 165:338.PubMedCrossRefGoogle Scholar
  20. 20.
    Jaeger, C. B., and Lund, R. D., 1980, Transplantation of embryonic occipital cortex to the brain of newborn rats: An autoradiographic study of transplant histogenesis, Exp. Brain Res. 40:265.PubMedCrossRefGoogle Scholar
  21. 21.
    Jaeger, C. B., and Lund, R. D., 1980, Transplantation of embryonic occipital cortex to the tectal region of newborn rats: A light microscopic study of organization and connectivity of the transplants, J. Comp. Neurol. 194:571.PubMedCrossRefGoogle Scholar
  22. 22.
    Das, G. D., Hallas, B. H., and Das, K. G., 1980, Transplantation of brain tissue in the brain of rat. I. Growth characteristics of neocortical transplants from embryos of different ages, Am. J. Anat. 158:135.PubMedCrossRefGoogle Scholar
  23. 23.
    McLoon, S. C., and Lund, R. D., 1980, Identification of cells in retinal transplants which project to host visual centers: A horseradish peroxidase study in rats, Brain Res. 197:491.PubMedCrossRefGoogle Scholar
  24. 24.
    McLoon, L. K., Lund, R. D., and McLoon, S. C., 1982, Transplantation of reaggregates of embryonic neural retinae to neonatal rat brain: Differentiation and formation of connections, J. Comp. Neurol. 205:179.PubMedCrossRefGoogle Scholar
  25. 25.
    Freed, W. J., and Wyatt, R. J., 1980, Transplantation of eyes to the adult rat brain: Histological findings and light-evoked potential response. Life Sci. 27:503.PubMedCrossRefGoogle Scholar
  26. 26.
    Graziadei, P. P. C., and Kaplan, M. S., 1980, Regrowth of olfactory sensory axons into transplanted neural tissue. 1. Development of connections with the occipital cortex, Brain Res. 201:39.PubMedCrossRefGoogle Scholar
  27. 27.
    Lund, R. D., and Harvey, A. R., 1981, Transplantation of tectal tissue in rats. I. Organization of transplants and pattern of distribution of host afferents within them, J. Comp. Neurol. 201:191.PubMedCrossRefGoogle Scholar
  28. 28.
    Sunde, N., and Zimmer, J., 1981, Transplantation of central nervous tissue: An introduction with results and implications, Acta Neurol. Scand. 63:323.PubMedGoogle Scholar
  29. 29.
    Wells, J., and McAllister, J. P., II, 1982, The development of cerebellar primordia transplanted to the neocortex of the rat, Dev. Brain Res. 4:167.CrossRefGoogle Scholar
  30. 30.
    Stenevi, U., Björklund, A., Kromer, L. F., Paden, C. M., Gerlach, J. L., McEwen, B. S., and Silverman, A. J., 1980, Differentiation of embryonic hypothalamic transplants cultured on the choroidal pia in brains of adult rats, Cell Tissue Res. 205:217.PubMedCrossRefGoogle Scholar
  31. 31.
    Stenevi, U., Björklund, A., and Svendgaard, N.-A., 1976, Transplantation of central and peripheral monoamine neurons to the adult rat brain: Techniques and conditions for survival, Brain Res. 114:1.PubMedCrossRefGoogle Scholar
  32. 32.
    Björklund, A., Stenevi, U., and Svendgaard, N.-A., 1976, Growth of transplanted monoaminergic neurons into the adult hippocampus along the perforant path, Nature (London) 262:787.CrossRefGoogle Scholar
  33. 33.
    Björklund, A., Segal, M., and Stenevi, U., 1979, Functional reinnervation of the rat hippocampus by locus coeruleus implants, Brain Res. 170:409.PubMedCrossRefGoogle Scholar
  34. 34.
    Björklund, A., and Stenevi, U., 1977, Reformation of the severed septohippocampal cholinergic pathway in the adult rat by transplanted septal neurons, Cell Tissue Res. 185:289.PubMedCrossRefGoogle Scholar
  35. 35.
    Møllgård, K., Lundberg, J. J., Beebe, B. K., Björklund, A., and Stenevi, U., 1978, The intracerebrally cultured ‘microbrain’: A new tool in developmental neurobiology, Neurosci. Lett. 8:295.PubMedCrossRefGoogle Scholar
  36. 36.
    Kromer, L. F., and Björklund, A., 1980, Embryonic neural transplants provide model systems for studying development and regeneration in the mammalian CNS, in: Multidisciplinary Approach to Brain Development (C. DiBenedetta, R. Balazs, G. Gombos, and G. Porcellati, eds.), pp. 409–426, Elsevier/ North-Holland, Amsterdam.Google Scholar
  37. 37.
    Kromer, L.F., Björklund, A., and Stenevi, U., 1979, Intracephalic implants: A technique for studying neuronal interactions, Science 204:1117.PubMedCrossRefGoogle Scholar
  38. 38.
    Alvarado-Mallart, R. M., and Sotelo, C., 1982, Differentiation of cerebellar anlage heterotopically transplanted to adult rat brain: A light and electron microscopic study, J. Comp. Neurol. 212:247.PubMedCrossRefGoogle Scholar
  39. 39.
    Kromer, L. F., Björklund, A., and Stenevi, U., 1981, Innervation of embryonic hippocampal implants by regenerating axons of cholinergic septal neurons in the adult rat, Brain Res. 210:153.PubMedCrossRefGoogle Scholar
  40. 40.
    Kromer, L. F., Björklund, A., and Stenevi, U., 1983, Intracephalic embryonic neural implants in the adult rat brain. I. Growth and mature organization of brainstem, cerebellar and hippocampal implants, J. Comp. Neurol. 218:433.PubMedCrossRefGoogle Scholar
  41. 41.
    Hallas, B. H., Das, G. D., and Das, K. G., 1980, Transplantation of brain tissue in the brain of rat. II. Growth characteristics of neocortical transplants in hosts of different ages, Am. J. Anat. 158:147.PubMedCrossRefGoogle Scholar
  42. 42.
    Gash, D., Sladek, J. R., Jr., and Sladek, C. D., 1980, Functional development of grafted vasopressin neurons, Science 210:1367.PubMedCrossRefGoogle Scholar
  43. 43.
    Altman, J., and Bayer, S. A., 1978, Prenatal development of the cerebellar system in the rat. I. Gytogenesis and histogenesis of the deep nuclei and the cortex of the cerebellum, J. Comp. Neurol. 179:23.PubMedCrossRefGoogle Scholar
  44. 44.
    Altman, J., and Bayer, S. A., 1980, Development of the brainstem in the rat. I. Thymidine-radiographic study of the time of origin of neurons of the lower medulla, J. Comp. Neurol. 194:1.PubMedCrossRefGoogle Scholar
  45. 45.
    Altman, J., and Bayer, S. A., 1980, Development of the brainstem in the rat. II. Thymidine-radiographic study of the time of origin of neurons of the upper medulla, excluding the vestibular and auditory nuclei, J. Comp. Neurol. 194:37.PubMedCrossRefGoogle Scholar
  46. 46.
    Altman, J., and Bayer, S. A., 1980, Development of the brainstem in the rat. III. Thymidine-radiographic study of the time of origin of neurons of the vestibular and auditory nuclei of the upper medulla, J. Comp. Neurol. 194:877.PubMedCrossRefGoogle Scholar
  47. 47.
    Altman, J., and Bayer, S. A., 1980, Development of the brainstem in the rat. IV. Thymidine-radiographic study of the time of origin of neurons in the pontine region, J. Comp. Neurol. 194:905.PubMedCrossRefGoogle Scholar
  48. 48.
    Kromer, L. F., 1982, Development of embryonic hippocampal transplants in the adult rodent CNS, Soc. Neurosci. Abstr. 8:327.Google Scholar
  49. 49.
    Das, G. D., 1982, Extrapharenchymal neural transplants: Their cytology and survivability, Brain Res. 241:182.PubMedCrossRefGoogle Scholar
  50. 50.
    Seiger, Ȧ., and Olson, L., 1973, Late prenatal ontogeny of central monoamine neurons in the rat: Fluorescence histochemical observations, Z. Anat. Entwicklungsgesch. 140:281.PubMedCrossRefGoogle Scholar
  51. 51.
    Lauder, J. M., and Bloom, F. E., 1974, Ontogeny of monoamine neurons in the locus coeruleus, raphe nuclei and substantia nigra of the rat. I. Cell differentiation, J. Comp. Neurol. 155:469.PubMedCrossRefGoogle Scholar
  52. 52.
    Sievers, J., Lolova, I., Jenner, S., Klemm, H. P., and Sievers, H., 1981, Morphological and biochemical studies on the ontogenesis of the nucleus locus coeruleus, Bibl. Anat. 19:52.PubMedGoogle Scholar
  53. 53.
    Levitt, P., Moore, R. Y., and Garber, B. B., 1976, Selective cell association of catecholamine neurons in brain aggregates in vitro, Brain Res. 111:311.PubMedCrossRefGoogle Scholar
  54. 54.
    Hemmendinger, L. M., Garber, B. B., Hoffman, P. C., and Heller, A., 1981, Selective association of embryonic murine mesencephalic dopamine neurons in vitro, Brain Res. 222:417.PubMedCrossRefGoogle Scholar
  55. 55.
    Crain, S. A., Peterson, E. R., and Bornstein, M. B., 1968, Formation of functional interneuronal connections between explants of various mammalian central nervous tissues during development in vitro, in: Ciba Foundation Symposium, Growth of the Nervous System (G. E. W. Wolstenholme and M. O’Connor, eds.), pp. 13–31, Churchill, London.Google Scholar
  56. 56.
    Bayer, S. A., 1980, Development of the hippocampal region in the rat. I. Neurogenesis examined with 3H-thymidine autoradiography, J. Comp. Neurol. 190:87.PubMedCrossRefGoogle Scholar
  57. 57.
    Bayer, S. A., 1980, Development of the hippocampal region in the rat. II. Morphogenesis during embryonic and early postnatal life, J. Comp. Neurol. 190:115.PubMedCrossRefGoogle Scholar
  58. 58.
    Schlessinger, A. R., Cowan, W. M., and Gottlieb, D. I., 1975, An autoradiographic study of the time of origin and the pattern of granule cell migration in the dentate gyrus of the rat, J. Comp. Neurol. 159:149.PubMedCrossRefGoogle Scholar
  59. 59.
    LaVail, J. H., and Wolf, M. K., 1973, Postnatal development of the mouse dentate gyrus in organotypic cultures of the hippocampal formation, Am. J. Anat. 137:47.PubMedCrossRefGoogle Scholar
  60. 60.
    Beach, R. L., Bathgate, S. L., and Cotman, C. W., 1982, Identification of cell types in rat hippocampal slices maintained in organotypic cultures, Dev. Brain Res. 3:3.CrossRefGoogle Scholar
  61. 61.
    Levitt, P., and Rakic, P., 1980, Immunoperoxidase localization of glial fibrillary acidic protein in radial giial cells and astrocytes of the developing rhesus monkey brain, J. Comp. Neurol. 193:815.PubMedCrossRefGoogle Scholar
  62. 62.
    DeLong, G. R., 1970, Histogenesis of fetal mouse isocortex and hippocampus in reaggregating cell cultures, Dev. Biol. 22: 563.PubMedCrossRefGoogle Scholar
  63. 63.
    Miale, I. L., and Sidman, R. S., 1961, An autoradiographic analysis of histogenesis in the mouse cerebellum, Exp. Neurol. 4:277.PubMedCrossRefGoogle Scholar
  64. 64.
    Altman, J., 1966, Autoradiographic and histological studies of postnatal neurogenesis. II. A longitudinal investigation of the kinetics, migration and transformation of cells incorporating tritiated thymidine in infant rats, with special reference to postnatal neurogenesis in some brain regions, J. Comp. Neurol. 128:431.CrossRefGoogle Scholar
  65. 65.
    Korneliussen, H. K., 1968, On the ontogenetic development of the cerebellum (nuclei, fissures and cortex) in the rat, with special reference to regional variations in corticogenesis, J. Hirnforsch. 10:379.PubMedGoogle Scholar
  66. 66.
    Rakic, P., 1971, Neuron—glia relationship during granule cell migration in developing cerebellar cortex: A Golgi and electron microscopic study in macacus rhesus, J. Comp. Neurol. 141:283.PubMedCrossRefGoogle Scholar
  67. 67.
    Wolf, M. K., 1964, Differentiation of neuronal types and synapses in myelinating cultures of mouse cerebellum, J. Cell Biol. 22: 259.PubMedCrossRefGoogle Scholar
  68. 68.
    Wolf, M. K., 1970, Anatomy of cultured mouse cerebellum. II. Organotypic migration of granule cells demonstrated by silver impregnation of normal and mutant cultures, J. Comp. Neurol. 140:281.PubMedCrossRefGoogle Scholar
  69. 69.
    Wolf, M. K., and Dubois-Dalcq, M., 1970, Anatomy of cultured mouse cerebellum. I. Golgi and electron microscopic demonstration of granule cells, their afferent and efferent synapses, J.Comp. Neurol. 140:261.PubMedCrossRefGoogle Scholar
  70. 70.
    Allerand, C. D., 1971, Patterns of neuronal differentiation in developing cultures of neonatal mouse cerebellum: A living and silver impregnation study, J. Comp. Neurol. 142:167.PubMedCrossRefGoogle Scholar
  71. 71.
    Seil, F. J., 1972, Neuronal groups and fiber patterns in cerebellar tissue cultures, Brain Res. 42:33.PubMedCrossRefGoogle Scholar
  72. 72.
    Hendelman, W. J., and Aggerwal, A. S., 1980, The Purkinje neuron. I. A Golgi study of its development in the mouse and in culture, J. Comp. Neurol. 193:1063.PubMedCrossRefGoogle Scholar
  73. 73.
    Calvet, M.-C., Lepault, A.-M., and Calvet, J., 1976, A procion yellow study of cultured Purkinje cells, Brain Res. 111:399.PubMedCrossRefGoogle Scholar
  74. 74.
    Sotelo, C., and Arsenio-Nunes, M. L., 1976, Development of Purkinje cells in absence of climbing fibers, Brain Res. 111:389.CrossRefGoogle Scholar
  75. 75.
    Nagai, T., Satoh, K., Imamoto, K., and Maeda, T., 1981, Divergent projections of catecholamine neurons of the locus coeruleus as revealed by fluorescent retrograde double labeling technique, Neurosci. Lett. 23:117.PubMedCrossRefGoogle Scholar
  76. 76.
    Harkmark, W., 1954, Cell migrations from the rhombic lip to the inferior olive, the nucleus raphe and the pons: A morphological and experimental investigation of chick embryos, J. Comp. Neurol. 100:115.PubMedCrossRefGoogle Scholar
  77. 77.
    Altman, J., and Bayer, S. A., 1978, Prenatal development of the cerebellar system in the rat. II. Cytogenesis and histogenesis of the inferior olive, pontine gray, and the precerebellar reticular nuclei, J. Comp. Neurol. 179:49.PubMedCrossRefGoogle Scholar
  78. 78.
    Mares, V., and Lodin, Z., 1970, The cellular kinetics of the developing mouse cerebellum. II. The function of the external granular layer in the process of gyrification, Brain Res. 23:343.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1984

Authors and Affiliations

  • Lawrence F. Kromer
    • 1
  1. 1.Department of Anatomy and Neurobiology, College of MedicineUniversity of VermontBurlingtonUSA

Personalised recommendations