Skip to main content
SpringerLink
Log in

Complex tight junctions of epithelial and of endothelial cells in early foetal brain

  • Published:
Journal of Neurocytology

Summary

The morphology of epithelial and of endothelial intercellular junctions in human foetal (9–15 weeks gestation) and sheep foetal (50, 60 and 125 days gestation, term 147 days) brain has been studied using the freeze-fracture technique and thin section transmission electronmicroscopy. Freeze-fracture replicas of the choroid plexus of both early human and sheep foetuses showed that the choroidal ependymal cells are linked at the ventricular surface by tight junctions. Freeze-fracture replicas of foetal cortical endothelial cell junctions showed that they are still more complex than those of choroidal epithelial cells, in all specimens so far examined. In some 60 day sheep foetuses the dye Alcian blue, which binds to plasma albumin and which is electrondense when treated with osmium tetroxide, was injected intravenously a few minutes prior to fixation. The dye penetrated from blood into brain extracellular space and c.s.f. but apparentlynot by anintercellular route. The dye was found in a tubular system (endoplasmic reticulum) in both choroidal epithelial and cortical endothelial cells. The possibility that protein penetrates into the foetal brain and c.s.f. by atranscellular route is discussed. The possible significance of these findings in relation to previous ideas and studies of the development of blood-brain barrier mechanisms is also considered.

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.

Similar content being viewed by others

References

  • Årnhold, R. G. andZetterström, R. (1958) Proteins in the c.s.f. in newborn. An electrophoretic study including haemolytic disease of the newborn.Pediatrics 21, 279–87.

    Google Scholar 

  • Aström, K.-E. (1967) On the early development of the isocortex in fetal sheep.Progress in Brain Research 26, 1–59.

    Google Scholar 

  • Bakay, L. (1953) Studies on blood-brain barrier with radioactive phosphorus. III. Embryonic development of the barrier.Archives of Neurology and Psychiatry 70, 30–9.

    Google Scholar 

  • Barcroft, J. (1938)The Brain and Its Environment. P. I. New Haven: Yale University Press.

    Google Scholar 

  • Behnsen, G. (1927) Über die Farbstoffspeicherung im Zentralnervensystem der Weissen Maus in verschiedenen Alterszuständen.Zeitschrift für Zellforschung und mikroskopische Anatomie 4, 515–72.

    Google Scholar 

  • Bohr, V. andMøllgård, K. (1974) Tight junctions in human fetal choroid plexus visualized by freeze-etching.Brain Research 81, 314–18.

    Google Scholar 

  • Bradbury, M. W. B., Crowder, J., Desai, S., Reynolds, J. M., Reynolds, M. andSaunders, N. R. (1972) Electrolytes and water in the brain and cerebrospinal fluid of the foetal sheep and guinea-pig.Journal of Physiology 227, 591–610.

    Google Scholar 

  • Branton, D. (1966) Fracture faces of frozen membranes.Proceedings of the National Academy of Sciences (Washington) 55, 1048–56.

    Google Scholar 

  • Brightman, M. W. andReese, T. S. (1969) Junctions between intimately apposed cell membranes in the vertebrate brain.Journal of Cell Biology 40, 648–77.

    Google Scholar 

  • Cameron, I. R., Davson, H. andSegal, M. B. (1969) The effect of hypercapnia on the blood-brain barrier to sucrose in the rabbit.Yale Journal of Biology and Medicine 42, 241–7.

    Google Scholar 

  • Claude, P. andGoodenough, D. (1973) Fracture faces of zonulae occludentes from ‘tight’ and ‘leaky’ epithelia.Journal of Cell Biology 58, 390–400.

    Google Scholar 

  • Connell, C. J. andMercer, K. L. (1974) Freeze-fracture appearance of the capillary endothelium in the cerebral cortex of mouse brain.American Journal of Anatomy 140, 595–9.

    Google Scholar 

  • Crone, C. (1965) The permeability of brain capillaries to non-electrolytes.Acta Physiologica Scandinavica 64, 407–17.

    Google Scholar 

  • Davson, H. (1967)Physiology of the Cerebrospinal Fluid. London: Churchill.

    Google Scholar 

  • Delorme, P. (1972) Différenciation ultrastructurale des jonctions intercellulaires de l'endothelium des capillaires téléncephaliques chez l'embryon de poulet.Zeitschrift für Zellforschung und mikroskopische Anatomie 133, 571–82.

    Google Scholar 

  • Delorme, P., Gayet, J. andGrignon, G. (1970) Ultrastructural study on transcapillary exchanges in the developing telencephalon of the chicken.Brain Research 22, 269–83.

    Google Scholar 

  • Durbin, G. M., Dziegielewska, K. M., Evans, C. A. N., Malinowska, D. H., Møllgård, K., Reynolds, E. O. R., Reynolds, J. M., Reynolds, M. L. andSaunders, N. R. (1975) Penetration of labelled protein from blood into foetal brain and c.s.f.Proceedings of the Physiological Society, Copenhagen (April)J. Physiol., in press.

  • Ehrlich, P. (1885)Das Sauerstoff Bedürfnis des Organismus. Eine fabenanalytische Studie, pp. 69–72, Berlin: Hirschwald.

    Google Scholar 

  • Evans, C. A. N., Reynolds, J. M., Reynolds, M. L., Saunders, N. R. andSegal, M. B. (1974) The development of a blood-brain barrier mechanism in foetal sheep.Journal of Physiology 238, 371–86.

    Google Scholar 

  • Friend, D. S. andGilula, N. B. (1972) Variations in tight and gap junctions in mammalian tissues.Journal of Cell Biology 53, 758–76.

    Google Scholar 

  • Frömter, E. andDiamond, J. (1972) Route of passive ion permeation in epithelia.Nature New Biology 235, 9–13.

    Google Scholar 

  • Gröntoft, O. (1954) Intracranial haemorrhage and blood-brain barrier problems in the newborn.Acta Pathologica et Microbiologica Scandinavica Supplementum C pp. 1–102.

  • Kreutziger, G. O. (1968) Freeze-etching of intercellular junctions of mouse liver. InProceedings of the 26th Meeting of the Electronmicroscopical Society of America pp. 234–235. Baton Rouge: La Claitor's Publishing Division.

    Google Scholar 

  • Klosovskii, B. N. (1963)The Development of the Brain and its Disturbance by Harmful Factors (Translated by Haigh, B.), p. 8. Oxford: Pergamon.

    Google Scholar 

  • Lee, J. C. (1971) Evolution in the concept of the blood-brain barrier phenomenon.Progress in Neuropathology 1, 84–145.

    Google Scholar 

  • Knutton, S., Limerick, A. R. andRobertson, J. D. (1974) Regular structures in membranes. I. Membranes in the endocytic complex of ileal epithelial cells.Journal of Cell Biology 62, 679–94.

    Google Scholar 

  • Moor, H. andMuhlethaler, K. (1968) Fine structure in frozen-etched yeast cells.Journal of Cell Biology 17, 609–28.

    Google Scholar 

  • Møllgård, K. andSørensen, S. C. (1974) The permeability of cerebral capillaries to a tracer molecule, Alcian blue, with a molecular weight of 1390. InThe Pathology of Cerebral Microcirculation (edited byJ. Cervos-Navarro), pp. 119–121, Berlin: Walter de Gruyter and Co.

    Google Scholar 

  • Näätänen, E. (1947) Ueber die Speicherung der intravenös injuzierten Methylenblaulösung in Zentralnervensystem des menschlichen Fetus.Acta Societatis medicorum fennicae ‘Duodecim’ 24, ii-ii.

    Google Scholar 

  • Pinto da Silva, P. andBranton, D. (1970) Membrane splitting in freeze-etching.Journal of Cell Biology 45, 598–605.

    Google Scholar 

  • Reese, T. A. andKarnovsky, M. J. (1967) Fine structural localization of a blood-brain barrier to exogenous peroxidase.Journal of Cell Biology 34, 207–17.

    Google Scholar 

  • Revel, J. P., Yip, P. andChang, I. L. (1973) Cell junctions in the early chick embryo—A freeze etch study.Developmental Biology 35, 302–17.

    Google Scholar 

  • Schultze, H. E. andHeremans, J. F. (1966)Molecular Biology of Human Proteins, with special reference to plasma proteins. Vol. 1, Nature and metabolism of extracellular proteins. Amsterdam: Elsevier.

    Google Scholar 

  • Staehelin, L. A. (1973) Further observations on the fine structure of freeze-cleaved tight junctions.Journal of Cell Science 13, 763–86.

    Google Scholar 

  • Tschirgi, R. D. (1950) Protein complexes and the impermeability of the blood-brain barrier to dyes.American Journal of Physiology 163, 756P.

    Google Scholar 

  • Wissig, S. L. andGraney, D. O. (1968) Membrane modifications in the apical endocytic complex of ileal epithelial cells.Journal of Cell Biology 39, 564–79.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The Laboratory of Electron Microscopy, Anatomy Department A, University of Copenhagen, Universitetsparken 1, 2100, Kobenhavn Ø, Denmark

    K. Møllgård

  2. Department of Physiology, University College London, Gower Street, WC1E 6BT, London, UK

    N. R. Saunders

Authors
  1. K. Møllgård
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. N. R. Saunders
    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

Møllgård, K., Saunders, N.R. Complex tight junctions of epithelial and of endothelial cells in early foetal brain. J Neurocytol 4, 453–468 (1975). https://doi.org/10.1007/BF01261375

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01261375

Keywords

Search

Navigation