Skip to main content
SpringerLink
Log in

Glial cell differentiation in neuron-free and neuron-rich regions

II. Early appearance of S-100 protein positive astrocytes in human fetal hippocampus

  • Published:
Anatomy and Embryology Aims and scope Submit manuscript

Summary

The development of the human fetal hippocampus and dentate gyros has been studied immunocytochemically. The first glial cells to appear are vimentin-positive radial glial cells. A gradual transition from vimentin to glial fibrillary acidic protein (GFAP) reactivity in the radial glial cells occurs at week 8. The GFAP-positive radial glial cells transform into astrocytes from week 14. A population of small S-100-positive somata which morphologically and spatially are distinct from GFAP-positive radial glial cells and their transformed progeny, are found as early as week 9.5 in the hippocampus during the period of peak neurogenesis. The well-defined immunoreactivity of the morphologically homogenous cell subpopulation for S-100 protein, which has been used as an astrocytic marker in the adult hippocampus, indicates that astrocytes may differentiate at very early gestational ages in human fetuses. The S-100-positive astrocytes are thought to be derived from ventricular zone cells, which at the time of their appearance do not express any of the applied astrocytic markers (S-100, GFAP, vimentin). It is suggested that the S-100-positive astrocytic cell population interacts with the first incoming projection fibers, so modulating the pattern of connectivity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Altman J, Bayer SA (1975) Postnatal development of the hippocampal dentate gyrus under normal and experimental conditions. In: Isaacson RL, Pribram KH (eds) The hippocampus I. Structure and development. Plenum Press, New York, pp 95–119

    Google Scholar 

  • Antanitus DS, Choi BH, Lapham LW (1976) The demonstration of glial fibrillary acidic protein in the cerebrum of the human fetus by indirect immunofluorescence. Brain Res 103:613–616

    PubMed  Google Scholar 

  • Borit A, McIntosh GC (1981) Myelin basic protein and glial fibrillary acidic protein in human fetal brain. Neuropathol Appl Neurobiol 7:279–287

    PubMed  Google Scholar 

  • Boyes BE, Kim SLY, Lee V, Sung SC (1986) Immunohistochemical co-localization of S-100b and the glial fibrillary acidic protein in rat brain. Neuroscience 17:857–865

    PubMed  Google Scholar 

  • Celio MR (1990) Calbindin D-28k and parvalbumin in the rat nervous system. Neuroscience 35:375–475

    PubMed  Google Scholar 

  • Choi BH (1988) Developmental events during the early stages of cerebral cortical neurogenesis in man. A correlative light, electron microscopic, immunohistochemical and Golgi study. Acta Neuropathol 75:441–447

    PubMed  Google Scholar 

  • Choi BH, Kim RC, Lapham LW (1983) Do radial glia give rise to both astroglial and oligodendroglial cells? Dev Brain Res 8:119–130

    Google Scholar 

  • Cocchia D (1981) Immunocytochemical localization of S-100 protein in the brain of adult rat. Cell Tissue Res 214:529–540

    PubMed  Google Scholar 

  • Culican SM, Baumrind NL, Yamamoto M, Pearlman AL (1988) Cortical radial glia: identification in tissue culture and evidence for their transformation to astrocytes. J Neurosci 10:684–692

    Google Scholar 

  • Donato R, Prestagiovanni B, Zelano G (1986) Identity between cytoplasmic and membrane-bound S-100 proteins purified from bovine and rat brain. J Neurochem 46:1333–1337

    PubMed  Google Scholar 

  • Duffy CJ, Rakic P (1983) Differentiation of granule cell dendrites in the dentate gyrus of the rhesus monkey: a quantitative Golgi study. J Comp Neurol 214:224–237

    PubMed  Google Scholar 

  • Eckenhoff MF, Rakic P (1984) Radial organization of the hippocampal dentate gyrus: a Golgi, ultrastructural, and immunocytochemical analysis in the developing rhesus monkey. J Comp Neurol 223:1–21

    PubMed  Google Scholar 

  • Elder GA, Major EO (1988) Early appearance of type II astrocytes in developing human fetal brain. Dev Brain Res 42:146–150

    Google Scholar 

  • Engel AK, Müller CM (1989) Postnatal development of vimentin-immunoreactive radial glial cells in the primary visual cortex of the cat. J Neurocytol 18:437–450

    PubMed  Google Scholar 

  • ffrench-Constant C, Raff MC (1986) The oligodendrocyte type-2 astrocyte cell lineage is specialized for myelination. Nature 323:335–338

    PubMed  Google Scholar 

  • Frederiksen K, McKay RDG (1988) Proliferation and differentiation of rat neuroepithelial precursor cells in vivo. J Neurosci 8:1144–1151

    PubMed  Google Scholar 

  • Gasser UE, Hatten ME (1990) Neuron-glia interactions of rat hippocampal cells in vitro: glial-guided neuronal migration and neuronal regulation of glial differentiation. J Neurosci 10:1276–1285

    PubMed  Google Scholar 

  • Goldman JE, Geier SS, Hirano M (1986) Differentiation of astrocytes and oligodendrocytes from germinal matrix cells in primary culture. J Neurosci 6:52–60

    PubMed  Google Scholar 

  • Gordon-Weeks PR (1989) GAP-43 - What does it do in the growth cone? Trends Neurosci 12:363–365

    PubMed  Google Scholar 

  • Hansen SH, Stagaard M, Møllgård K (1989) Neurofilament-like pattern of reactivity in human foetal PNS and spinal cord following immunostaining with polyclonal anti-glial fibrillary acidic protein antibodies. J Neurocytol 18:427–436

    PubMed  Google Scholar 

  • Hatten ME (1990) Riding the glial mono-rail: a common mechanism for glial guided neuronal migration in different regions of the developing mammalian brain. Trends Neurosci 13:179–184

    PubMed  Google Scholar 

  • Hines M (1922) Studies of the growth and differentiation of the telencephalon in man. The fissura hippocampi. J Comp Neurol 34:73–171

    Google Scholar 

  • Hirano M, Goldman JE (1988) Gliogenesis in rat spinal cord: evidence for origin of astrocytes and oligodendrocytes from radial precursors. J Neurosci Res 21:155–167

    PubMed  Google Scholar 

  • Hockheld S, McKay RDG (1985) Identification of major cell classes in the developing mammalian nervous system. J Neurosci 12:3310–3328

    Google Scholar 

  • Humphrey T (1966a) Correlations between the development of the hippocampal formation and the differentiation of the olfactory bulbs. Ala J Med Sci 3:235–269

    PubMed  Google Scholar 

  • Humphrey T (1966 b) The development of the human hippocampal formation correlated with some aspects of its phylogenetic history. In: Hassler R, Stephan H (eds) Evolution of the forebrain. Plenum Press, New York, pp 104–116

    Google Scholar 

  • Hutchins JB, Casagrande VA (1989) Vimentin: changes in distribution during brain development. Glia 2:55–66

    PubMed  Google Scholar 

  • Hutchins KD, Dickson DW, Rashbaum WK, Lyman WD (1990) Localization of morphologically distinct microglial populations in the developing human fetal brain: implications for ontogeny. Dev Brain Res 55:95–102

    Google Scholar 

  • Ishikawa H, Nogami H, Shirasawa N (1983) Novel clonal strains from adult rat anterior pituitary producing S-100 protein. Nature 303:711–713

    PubMed  Google Scholar 

  • Kostović I, Seress L, Mrzljak L, Judag M (1989) Early onset of synapse formation in the human hippocampus. a correlation with Nissl-Golgi architectonics in 15- and 16.5-weeks-old fetuses. Neuroscience 30:105–116

    PubMed  Google Scholar 

  • Landry CF, Ivy GO, Dunn RJ, Marks A, Brown IR (1989) Expression of the gene encoding theβ-subunit of S-100 protein in the developing rat brain analyzed by in situ hybridization. Mol Brain Res 6:251–262

    PubMed  Google Scholar 

  • Lauriola L, Coli D, Cocchia D, Tallini G, Michetti F (1987) Comparative study by S-100 and GFAP immunohistochemistry of glial cell populations in the early stages of human spinal cord development. Dev Brain Res 37:251–255

    Google Scholar 

  • LeVine SM, Goldman JE (1988) Embryonic divergence of oligodendrocyte and astrocyte lineages in developing rat cerebrum. J Neurosci 8: 3992–4006

    PubMed  Google Scholar 

  • Levitt P, Rakic P (1980) Immunoperoxidase localization of glial fibrillary acidic protein in radial glial cells and astrocytes of the developing rhesus monkey brain. J Comp Neurol 193:815–840

    PubMed  Google Scholar 

  • Levitt P, Cooper ML, Rakic P (1981) Coexistence of neuronal and glial precursor cells in the cerebral ventricular zone of the fetal monkey: an ultrastructural immunoperoxidase analysis. J Neurosci 1: 27–39

    PubMed  Google Scholar 

  • Levitt P, Cooper ML, Rakic P (1983) Early divergence and changing proportions of neuronal and glial precursor cells in the primate cerebral ventricular zone. Dev Biol 96:472–484

    PubMed  Google Scholar 

  • Ludwin SK, Kosek JC, Eng LF (1976) The topographical distribution of S-100 and GFA proteins in the adult rat brain: an immunohistochemical study using horseradish peroxidase-labelled antibodies. J Comp Neurol 165:197–208

    PubMed  Google Scholar 

  • Matus A, Mughal S (1975) Immunohistochemical localisation of S-100 protein in brain. Nature 258:746–748

    PubMed  Google Scholar 

  • Møllgård K, Balslev Y (1989) The subcellular distribution of transferrin in rat choroid plexus studied with immunogold labelling of ultracryosections. Histochem J 21:441–448

    Google Scholar 

  • Nowakowski RS, Rakic P (1981) The site of origin and route and rate of migration of neurons to the hippocampal region of the rhesus monkey. J Comp Neurol 196:129–154

    PubMed  Google Scholar 

  • Rakic P (1971) Guidance of neurons migrating to the fetal monkey neocortex. Brain Res 33:471–476

    PubMed  Google Scholar 

  • Rakic P (1984) Emergence of neuronal and glial cell lineages in primate brain. In: Black IB (ed) Cellular and molecular biology of neuronal development. Plenum Press, New York, pp 29–50

    Google Scholar 

  • Rakic P, Nowakowski RS (1981) The time of origin of neurons in the hippocampal region of the rhesus monkey. J Comp Neurol 196:99–128

    PubMed  Google Scholar 

  • Reske-Nielsen E, Oster S, Reintoft I (1987) Astrocytes in the prenatal central nervous system. Acta Pathol Microbiol Immunol Scand, Sect A 95:339–346

    Google Scholar 

  • Rickmann M, Amaral DG, Cowan WM (1987) Organization of radial glial cells during the development of the rat dentate gyrus. J Comp Neurol 264:449–479

    PubMed  Google Scholar 

  • Roessmann U, Gambetti P (1986) Astrocytes in the developing human brain. Acta Neuropathol 70:308–313

    PubMed  Google Scholar 

  • Rogers J (1989) Calcium-binding proteins: the search for functions. Nature 339:661–662

    Google Scholar 

  • Rolland B, Le Prince G, Fages C, Nunez J, Tardy M (1990) GFAP turnover during astroglial proliferation and differentiation. Dev Brain Res 56:144–149

    Google Scholar 

  • Sasaki A, Hirato J, Nakazato Y, Ishda Y (1988) Immunohistochemical study of the early human fetal brain. Acta NeuroPathol 76:128–134

    PubMed  Google Scholar 

  • Schmechel DE, Rakic P (1979a) Arrested proliferation of radial glial cells during midgestation in rhesus monkey. Science 277:303–305

    Google Scholar 

  • Schmechel DE, Rakic P (1979b) A Golgi study of radial glial cells in developing monkey telencephalon: morphogenesis and transformation into astrocytes. Anat Embryol 156:115–152

    PubMed  Google Scholar 

  • Schmechel DE, Marangos PJ, Brightman M (1978) Neurone-specific enolase is a molecular marker for peripheral and central neuroendocrine cells. Nature 276:834–836

    PubMed  Google Scholar 

  • Schmidt-Kastner R, Szymas J (1990) Immunohistochemistry of glial fibrillary acidic protein, vimentin and S-100 protein for study of astrocytes in hippocampus of rat. J Chem Neuroanat 3:179–192

    PubMed  Google Scholar 

  • Seto-Ohshima A, Yamazaki Y,Kawamura N, Kitajuma S, Sano M, Mizutani A (1987) The early expression of immunoreactivity for calmodulin in the nervous system of mouse embryos. Histochemistry 86:337–343

    PubMed  Google Scholar 

  • Shinohara H, Semba R, Kato K, Kashiwamata S, Tanaka O (1986) Immunohistochemical localization of gamma-enolase in early human embryos. Brain Res 282:33–38

    Google Scholar 

  • Stagaard M, Møllgård K (1989) The developing neuroepithelium in human embryonic and fetal brain studied with vimentin-immunocytochemistry. Anat Embryol 180:17–28

    PubMed  Google Scholar 

  • Stagaard M, Nowakowski RS, Møllgård K (1990) S-100 immuno-reactivity is differentially localized during the development of neuron-free and neuron-rich areas (abstract). Eur J Neurosci [Suppl 3]:223

    Google Scholar 

  • Stagaard Janas M, Nowakowski RS, Terkelsen OBF, Møllgård K (1991) Glial cell differentiation in neuron-free and neuron-rich regions. I. Selective appearance of S-100 protein in radial glial cells of the hippocampal fimbria in human fetuses. Anat Embryol 184:549–558

    PubMed  Google Scholar 

  • Takahashi T, Misson JP, Caviness VS (1990) Glial process elongation and branching in the developing murine neocortex — a qualitative and quantitative immunohistochemical analysis. J Comp Neurol 302:15–28

    PubMed  Google Scholar 

  • Thompson RJ, Doran JF, Jackson P, Dhillon AP, Rode J (1983) PGP 9.5 — A new marker for vertebrate neurones and neuroendocrine cells. Brain Res 278:224–228

    PubMed  Google Scholar 

  • Voigt T (1989) Development of glial cells in the cerebral wall of ferrets: direct tracing of their transformation from radial glia into astrocytes. J Comp Neurol 289:74–88

    Google Scholar 

  • Wilkinson M, Hume R, Strange R, Bell JE (1990) Glial and neuronal differentiation in the human fetal brain 9–23 weeks of gestation. Neuropathol Appl Neurobiol 16:493–204

    Google Scholar 

  • Winningham-Major F, Staecker JL, Barger SW, Coats S, van Eldik LJ (1989) Neurite extension and neuronal survival activities of recombinant S100β proteins that differ in the content and position of cysteine residues. J Cell Biol 109:3063–3071

    Google Scholar 

  • Yakolev PL, Lecours A-R (1967) The myelogenetic cycles of regional maturation of the brain. In: Minowski A (ed) Regional development of the brain in early foetal life. Blackwell, London, pp 3–70

    Google Scholar 

  • Zuckerman JE, Herschman JR, Levine L (1970) Appearance of a brain specific antigen (the S-100 protein) during human foetal development. J Neurochem 17:247–251

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Medical Anatomy A, and Neuroscience Center, Panum Institute, University of Copenhagen, Blegdamsvej 3, DK-2200, Copenhagen N, Denmark

    Mette Stagaard Janas & Kjeld Møllgård

  2. Department of Neuroscience and Cell Biology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, 08854, Piscataway, NJ, USA

    Richard S. Nowakowski

Authors
  1. Mette Stagaard Janas
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Richard S. Nowakowski
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kjeld Møllgård
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Janas, M.S., Nowakowski, R.S. & Møllgård, K. Glial cell differentiation in neuron-free and neuron-rich regions. Anat Embryol 184, 559–569 (1991). https://doi.org/10.1007/BF00942578

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00942578

Key words

Search

Navigation