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Patterns of glial development in the human foetal spinal cord during the late first and second trimester


Although the presence of radial glia, astrocytes, oligodendrocytes and microglia has been reported in the human foetal spinal cord by ten gestational weeks, neuroanatomic studies employing molecular probes that describe the interrelated development of these cells from the late first trimester through the late second trimester are few. In this study, immunocytochemical methods using antibodies to vimentin and glial fibrillary acidic protein were used to identify radial glia and/or astrocytes. An antibody to myelin basic protein was used for oligodendrocytes and myelin; and, an antibody to phosphorylated high and medium molecular weight neurofilaments identified axons. Lectin histochemistry usingRicinus communis agglutinin-I was employed to identify microglia. Vibratome sections from 35 human foetal spinal cord ranging in age from 9–20 gestation weeks were studied. By 12 gestational weeks, vimentin-positive radial glia were present at all three levels of the spinal cord. Their processes were easily identified in the dorsal two-thirds of cord sections, and reaction product for vimentin was more intense at cervical and thoracic levels than lumbosacral sections. By 15 gestational weeks, vimentin-positive processes were radially arranged in the white matter. At this time, glial fibrillary acidic protein-positive astrocytes were more obvious in both the anterior and anterolateral funiculi than in the dorsal funiculus, and the same rostral to caudal gradient was seen for glial fibrillary acidic protein as it was for vimentin. Myelin basic protein expression followed similar temporal and spatial patterns.Ricinus communis agglutinin-I labelling revealed more microglia in the white matter than in grey matter throughout the spinal cord from 10–20 gestational weeks. By 20 gestational weeks, the gradients of glial fibrillary acidic protein and vimentin expression were more difficult to discern. White matter contained more microglia than grey matter. These results suggest that astrocytes as well as oligodendrocytes follow anterior-to-posterior and rostral-to-caudal developmental patterns in the human foetus during middle trimester development.

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  1. Antanitus, D. S., Choi, B. H. &Lapham, L. W. (1976) The demonstration of glial fibrillary acidic protein in the cerebrum of the human fetus by indirect immunofluorescence.Brain Research 103, 613–16.

  2. Bandtlow, C., Zachleder, T. &Schwab, M. E. (1990) Oligodendrocytes arrest neurite growth by contact inhibition.Journal of Neuroscience 10, 3837–48.

  3. Barres, B. A. &Raff, M. C. (1993) Proliferation of oligodendrocyte precursor cells depends on electrical activity in axons.Nature 361, 258–60.

  4. Bensted, J. P. M., Dobbing, J., Morgan, R. S., Reid, R. T. W. &Wright, G. P. (1957) Neuroglial development and myelination in the spinal cord of the chick embryo.Journal of Embryology and Experimental Morphology 5, 428–37.

  5. Choi, B. H. (1981) Radial glia of developing human fetal spinal cord: Golgi, immunohistochemical and electron microscopic study.Developmental Brain Research 1, 249–67.

  6. Choi, B. H. &Kim, R. C. (1984) Expression of glial fibrillary acidic protein in immature oligodendroglia.Science 223, 407–9.

  7. Choi, B. H. &Kim, R. C. (1985) Expression of glial fibrillary acidic protein by immature oligodendroglia and its implications.Journal of Neuroimmunology 8, 215–35.

  8. Choi, B. H. &Lapham, L. W. (1978) Radial glia in the human fetal cerebrum: a combined Golgi, immunofluorescent and electron microscopic study.Brain Research 148, 295–311.

  9. Dahl, D. (1981) The vimentin-GFA protein transition in rat neuroglia cytoskeleton occurs at the time of myelination.Journal of Neuroscience Research 6, 741–8.

  10. Esiri, M. M., Al Izzi, M. S. &Reading, M. C. (1991) Macrophages, microglial cells, and HLA-DR antigens in fetal and infant brain.Journal of Clinical Pathology 44, 102–6.

  11. Ghooray, G. T. &Martin, G. F. (1993) Development of radial glia and astrocytes in the spinal cord of the North American opossum (Didelphis virginiana): an immunohistochemical study using anti-vimentin and anti-glial fibrillary acidic protein.Glia 9, 1–9.

  12. Goldman, J. E. (1992) Regulation of oligodendrocyte differentiation.Trends in Neuroscience 15, 359–62.

  13. Guilian, D., Johnson, B., Krebs, J. F., Tapscott, M. J. &Honda, S. (1991) A growth factor from neuronal cell lines stimulates myelin protein synthesis in mammalian brain.Journal of Neuroscience 11, 327–36.

  14. Hern, W. M. (1984) Correlation of fetal age and measurements between 10 and 26 weeks of gestation.Obstetrics and Gynecology 63, 26–32.

  15. Hutchins, K. D., Dickson, D. W., Rashbaum, W. K. &Lyman, W. D. (1990) Localization of morphologically distinct microglial populations in the developing human fetal brain: implications for ontogeny.Developmental Brain Research 55, 95–102.

  16. Hutchins, K. D., Dickson, D. W., Rashbaum, W. K. &Lyman, W. D. (1992) Localization of microglia in the human fetal cervical spinal cord.Developmental Brain Research 66, 270–3.

  17. Ksiezak-Reding, H., Dickson, D. W., Davies, P. &Yen, S.-H. (1987) Recognition of tau epitopes by anti-neurofilament antibodies that stain Alzheimer neurofibrillary tangles.Proceedings of the National Academy of Sciences (USA) 84, 3410–14.

  18. Levitt, P. &Rakic, P. (1980) Immunoperoxidase localization of glial fibrillary acidic protein in radial glial cells and astrocytes of the developing rhesus monkey brain.Journal of Comparative Neurology 193, 815–40.

  19. Ling, E-A. &Wong, W-C. (1993) The origin and nature of ramified and amoeboid microglia: a historical review and current concepts.Glia 7, 9–18.

  20. Mayer, M., Bogler, O. &Noble, M. (1993) The inhibition of oligodendrocytic differentiation of O-2A progenitors caused by basic fibroblast growth factor is overridden by astrocytes.Glia 8, 12–19.

  21. Mcphilemy, K., Griffiths, I. R., Mitchell, L. S. &Kennedy, P. G. E. (1991) Loss of axonal contact causes down-regulation of the PLP gene in oligodendrocytes: evidence from partial lesions of the optic nerve.Neuropathology and Applied Neurobiology 17, 275–87.

  22. Mcphilemy, K., Mitchell, L. S., Griffiths, I. R., Morrison, S., Deary, A. W., Sommer, I. &Kennedy, P. G. E. (1990) Effect of optic nerve transection upon myelin protein gene expression by oligodendrocytes: evidence for axonal influences on gene expression.Journal of Neurocytology 19, 494–503.

  23. Meyer, S. A., Ingraham, C. A. &Mccarthy, K. D. (1989) Expression of vimentin by cultured astroglia and oligodendroglia.Journal of Neuroscience Research 24, 251–9.

  24. Nordlund, M., Hong, D., Fei, X. &Ratner, N. (1992) Schwann cells and cells in the oligodendrocyte lineage proliferate in response to a 50,000 dalton membrane-associated mitogen present in developing brain.Glia 5, 182–192.

  25. Pixley, S. K. R. &De Vellis, J. (1984) Transition between immature radial glia and mature astrocytes studies with a monoclonal antibody to vimentin.Developmental Brain Research 15, 201–9.

  26. Polak, J. M. &Van Noorden, S., eds. (1983)Immunocytochemistry. Practical applications in pathology and biology. Bristol: John Wright and Sons Ltd.

  27. Polak, M., Haymaker, W., Johnson, J. E. &D'amelio, F. (1982) Neuroglia and their reactions. In:Histology and histopathology of the nervous system (edited byHaymaker, W. &Adams, R. D.) pp. 363–480. Springfield: Charles C. Thomas.

  28. Richardson, W. D., Pringle, N., Mosley, M. J., Westermark, B. &Dubois-Dalcq, M. (1988) A role for platelet-derived growth factor in normal gliogenesis in the central nervous system.Cell 53, 309–19.

  29. Sasaki, A., Hirato, J., Nakazato, Y. &Ishida, Y. (1988) Immunohistochemical study of the early human fetal brain.Acta Neuropathology 76, 128–34.

  30. Schwab, M. E. (1990) Myelin-associated inhibitors of neurite growth and regeneration in the CNS.Trends in Neuroscience 13, 452–6.

  31. Sidman, R. L. &Rakic, P. (1982) Development of the human central nervous system. In:Histology and histopathology of the nervous system (edited byHaymaker, W. &Adams, R. D.) pp. 3–145. Springfield: Charles C. Thomas.

  32. Sternberger, L. A. &Sternberger, N. H. (1983) Monoclonal antibodies distinguish phosphorylated and nonphosphorylated forms of neurofilamentsin situ.Proceedings of the National Academy of Sciences (USA) 80, 6126–30.

  33. Tohyama, T., Lee, V. M.-Y., Rorke, L. B. &Trojanowski, J. Q. (1991) Molecular milestones that signal axonal maturation and the commitment of human spinal cord precursor cells to the neuronal or glial phenotype in development.Journal of Comparative Neurology 310, 1–15.

  34. Trapp, B. D., Moench, T., Pulley, M., Barbosa, E., Tennekoon, G. &Griffin, J. (1987) Spatial segregation of mRNA encoding myelin-specific proteins.Proceedings of the National Academy of Sciences (USA) 34, 7773–7.

  35. Weidenheim, K. M., Kress, Y., Epshteyn, I., Rashbaum, W. K. &Lyman, W. D. (1992) Early myelination in the human fetal lumbosacral spinal cord: characterization by light and electron microscopy.Journal of Neuropathology and Experimental Neurology 51, 142–9.

  36. Weidenheim, K. M., Epshteyn, I., Rashbaum, W. K. &Lyman, W. D. (1993) Neuroanatomical localization of myelin basic protein in the late first and early second trimester human fetal spinal cord and brainstem.Journal of Neurocytology 22, 507–16.

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Correspondence to K. M. Weidenheim.

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Weidenheim, K.M., Epshteyn, I., Rashbaum, W.K. et al. Patterns of glial development in the human foetal spinal cord during the late first and second trimester. J Neurocytol 23, 343–353 (1994).

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  • White Matter
  • Glial Fibrillary Acidic Protein
  • Myelin Basic Protein
  • Radial Glia
  • Vimentin Expression