Skip to main content
Log in

PCNA-binding to DNA at the G1/S transition in proliferating cells of the developing cerebral wall

  • Published:
Journal of Neurocytology

Summary

Proliferating cell nuclear antigen is a nuclear protein essential to DNA synthesis in eukaryotic cells. It is known to form part of a multi-protein complex which binds to DNA from the outset of S-phase of the cell cycle. We define in this analysis the interval of proliferating cell nuclear antigen binding to DNA (strictly speaking, the interval through which proliferating cell nuclear antigen is stained immunohistochemically after ethanol fixation) with respect to the stages of the cell cycle in the intact mammalian brain. The epithelium of the developing cerebral wall is favourable for such an analysis because nuclei at the same stage of the cell division cycle are spatially aligned with each other at the same depth of the epithelium. Therefore spatial location of a nucleus within the epithelium is a reliable indicator of the stage of the cell cycle for that nucleus. Proliferating cell nuclear antigen-DNA binding in this epithelium is initiated in the final 5% (26 min) of G1-phase and continues through the initial 35% (1.3 h) of S-phase. This phasic pattern of proliferating cell nuclear antigen-DNA binding, as revealed for the first time in the intact cerebral wall, approximates closely the phasic pattern as it has been characterized until now onlyin vitro in vertebrate cell lines. This analysis illustrates the potential of the cerebral proliferative epithelium for study of the molecular events of the cell cycle underin vivo conditions of histogenetic regulation.

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

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

  • Angevine, J. B. &Sidman, R. L. (1961) Autoradiographic study of cell migration during histogenesis of the cerebral cortex in the mouse.Nature 192, 766–8.

    Google Scholar 

  • Baserga, R. (1985)The Biology of Cell Reproduction. Cambridge: Harvard University Press.

    Google Scholar 

  • Bravo, R., Frank, R., Blundell, P. A. &Macdonald-Bravo, H. (1987) Cyclin/PCNA is the auxiliary protein of DNA polymerase-delta.Nature 326, 515–17.

    Google Scholar 

  • Bravo, R. &Macdonald-Bravo, H. (1987) Existence of two populations of cyclin/proliferating cell nuclear antigen during the cell cycle. Association with DNA replication sites.Journal of Cell Biology 105, 1549–54.

    Google Scholar 

  • Caviness, V. S., Jr (1982) Neocortical histogenesis in normal and reeler mice: a developmental study based upon [3H]thymidine autoradiography.Developmental Brain Research 4, 293–302.

    Google Scholar 

  • Celis, J. E. &Celis, A. (1985) Cell cycle-dependent variations in the distribution of the nuclear protein cyclin proliferating cell nuclear antigen in cultured cells: subdivision of S-phase.Proceedings of the National Academy of Sciences (USA)82, 3262–6.

    Google Scholar 

  • Chang, C., Ottavio, L., Travali, S., Lipson, K. E. &Baserga, R. (1990) Transcriptional and posttranslational regulation of the proliferating cell nuclear antigen gene.Molecular and Cellular Biology 10, 3289–96.

    Google Scholar 

  • Cross, F., Roberts, J. &Weintraub, H. (1989) Simple and complex cell cycles. InAnnual Review of Cell Biology (edited byPalade, G. E., Alberts, B. M. &Spudich, J. A.) pp. 341–96. Palo Alto: Annual Reviews Inc.

    Google Scholar 

  • Fangman, W. L. &Brewer, B. J. (1992) A question of time: replication origins of eukaryotic chromosomes.Cell 71, 363–6.

    Google Scholar 

  • Fox, M. H., Arndt-Jovin, D. J., Jovin, T. M., Baumann, P. H. &Robert-Nicoud, M. (1991) Spatial and temporal distribution of DNA replication sites localized by immunofluorescence and confocal microscopy in mouse fibroblasts.Journal of Cell Science 99, 247–53.

    Google Scholar 

  • Humbert, C., Santisteban, M. S., Usson, Y. &Robert-Nicoud, M. (1992) Intranuclear co-localization of newly replicated DNA and PCNA by simultaneous immunofluorescent labelling and confocal microscopy in MCF-7 cells.Journal of Cell Science 103, 97–103.

    Google Scholar 

  • Kill, I. R., Bridger, J. M., Campbell, K. H. S., Maldonaldo-Codina, G. &Hutchinson, C. J. (1992) The timing of the formation and usage of replicase clusters in S-phase nuclei of human diploid fibroblasts.Journal of Cell Science 100, 869–76.

    Google Scholar 

  • Lee, S. &Hurwitz, J. (1990) Mechanism of elongation of primed DNA by DNA polymerase delta, proliferating cell nuclear antigen, and activator 1.Journal of Biological Chemistry 87, 5672–6.

    Google Scholar 

  • Marin-Padilla, M. (1971) Early prenatal ontogenesis of the cerebral cortex (neocortex) of the cat (Felis domestica). A Golgi study. I. The primordial neocortical organization.Zeitschrift für Anatomie und Entwicklungsgeschichte 134, 117–45.

    Google Scholar 

  • McConnell, S. K. (1991) The generation of neuronal diversity in the central nervous system. InAnnual Review of Neuroscience (edited byCowan, W. M., Shooter, E. M., Stevens, C. F. &Thompson, R. F.) pp. 269–300. Palo Alto: Annual Reviews, Inc.

    Google Scholar 

  • Murray, A. &Kirschner, M. W. (1991) What controls the cell cycle.Scientific American 264, 56–63.

    Google Scholar 

  • Nowakowski, R. S., Lewin, S. B. &Miller, M. W. (1989) Bromodeoxyuridine immunohistochemical determination of the lengths of the cell cycle and the DNA-synthetic phase for an anatomically defined population.Journal of Neurocytology 18, 311–18.

    Google Scholar 

  • Nurse, P. (1990) Universal control mechanism regulating onset of M phase.Nature 344, 503–8.

    Google Scholar 

  • Olashaw, N. E., Olson, J. E., Drozdoff, V. &Pledger, W. J. (1992) Growth factors: their role in the control of cell proliferation. InMolecular and Cellular Approaches to the Control of Proliferation and Differentiation (edited byStein, G. S. &Lian, J. B.) pp. 3–27. New York: Academic Press.

    Google Scholar 

  • Pardee, A. B. (1987) The yang and yin of cell proliferation: An overview.Journal of Cell Physiology (Suppl)5, 107–10.

    Google Scholar 

  • Prelich, G., Kostura, M., Marshak, D. R., Mathews, M. B. &Stillman, B. (1987) The cell-cycle regulated proliferating cell nuclear antigen is required for SV40 DNA replication in vitro.Nature 326, 471–5.

    Google Scholar 

  • Prelich, G. &Stillman, B. (1988) Coordinated leading and lagging strand synthesis during SV40 DNA replicationin vitro requires PCNA.Cell 53, 117–26.

    Google Scholar 

  • Sauer, F. C. (1935) Mitosis in the neural tube.Journal of Comparative Neurology 62, 377–405.

    Google Scholar 

  • Sauer, F. C. (1936) The interkinetic migration of embryonic epithelial nuclei.Journal of Morphology 60, 1–11.

    Google Scholar 

  • Sauer, M. E. &Walker, B. E. (1959) Radioautographic study of interkinetic nuclear migration in the neural tube.Proceedings of the Society for Experimental Biology 101, 557–60.

    Google Scholar 

  • Sidman, R. L., Miale, I. L. &Feder, N. (1959) Cell proliferation and migration in the primitive ependymal zone: an autoradiographic study of histogenesis in the nervous system.Experimental Neurology 1, 322–33.

    Google Scholar 

  • Sidman, R. L. &Rakic, P. (1973) Neuronal migration, with special reference to developing human brain: a review.Brain Research 62, 1–35.

    Google Scholar 

  • Sidman, R. L. &Rakic, P. (1982) Development of the human central nervous system. InHistology and Histopathology of the Nervous System (edited byHaymaker, W. &Adams, R. D.) pp. 3–145. Springfield: Charles C Thomas.

    Google Scholar 

  • Takahashi, T., Nowakowski, R. S. &Caviness, V. S., Jr (1991) Cell output of the ventricular zone of the E14 mouse neocortex.Society for Neuroscience Abstracts 17, 29.

    Google Scholar 

  • Takahashi, T., Nowakowski, R. S. &Caviness, V. S., Jr (1992) BUdR as an S-phase marker for quantitative studies of cytokinetic behaviour in the murine cerebral ventricular zone.Journal of Neurocytology 21, 185–97.

    Google Scholar 

  • Takahashi, T., Nowakowski, R. S. &Caviness, V. S., Jr (1993) Cell cycle parameters and patterns of nuclear movement in the neocortical proliferative zone of the fetal mouse.Journal of Neuroscience 13, 820–33.

    Google Scholar 

  • Vriz, S., Lemaitre, J., Leibovici, M., Thierry, N. &Mechali, M. (1992) Comparative analysis of the intra-cellular localization of c-Myc, c-Fos, and replicative proteins during cell cycle progression.Molecular and Cellular Biology 12, 3548–55.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Takahashi, T., Caviness, V.S. PCNA-binding to DNA at the G1/S transition in proliferating cells of the developing cerebral wall. J Neurocytol 22, 1096–1102 (1993). https://doi.org/10.1007/BF01235751

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01235751

Keywords

Navigation