Summary
Cytophotometric measurements reveal that a temporally coordinate accumulation of histones and DNA occurs in rat cortex neurons between the last gestational day and the end of the third postnatal week. A rapid rise of both constituents around birth is followed by a more protracted synthesis. This leads to adult histone and DNA levels of approximately 3.3 arbitrary units as compared with 2 arbitrary units found in neuronal precursor cells at all foetal stages and in reference diploid nuclei from glia and liver. A secondary DNA increase in the fourth postnatal week, previously suspected on the basis of cytofluorometric measurements using the Schifftype stain BAO (bis-[4-aminophenyl]-1,3,4-oxadiazole), is not substantiated by the present work. This derives from the finding that alternative cytophotometric DNA measurements (ultraviolet absorption scanning) and autoradiographs of neuronal nuclei following repeated injections of [3H]thymidine into the lateral ventricles during the relevant period give no evidence of a further DNA increase after the third postnatal week. Neither does the accumulation of histones (measured by sulfaflavine cytofluorometry) continue beyond day 21. This leads us to conclude that DNA and histone syntheses cease at the end of the third week. Electrophoretic analyses of the histones show that the relative histone composition changes only slightly during neuronal development. Apart from an increase in the ratio of the histones H1o:H1 around birth no developmental alterations in histone composition are detectable.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Adamson, E.D., Woodland, H.R.: Histone synthesis in early amphibian development: Histone and DNA syntheses are not coordinated. J. Mol. Biol. 88, 263–285 (1974)
Altman, J.: DNA metabolism and cell proliferation. In: Handbook of neurochemistry A. Lajtha (ed.), pp. 137–182. New York: Plenum Press 1969
Berdnikov, V.A., Gorel, F.I., Sharypov, V.F.: Changes in subfraction composition of chicken lysine-rich histone during ontogenesis (In Russian). Biochimiya (Moscow) 41, 847–853 (1976), cited by Medvedev, Zh.A., Medvedeva, M.N., Robson, L. Tissue specificity and age changes of the pattern of the H1 group of histones in chromatin from mouse tissue. Gerontology 24, 286–292 (1978)
Blobel, G., Potter, V.R.: Nuclei from rat liver: Isolation method that combines purity with high yield. Science 154, 1662–1665 (1966)
Borun, T.W., Scharff, M.D., Robbins, E.: Rapidly labeled, polyribosome-associated RNA having the properties of histone messenger. Proc. Natl. Acad. Sci. USA 58, 1977–1983 (1967)
Bregnard, A., Knüsel, A., Kuenzle, C.C.: Are all the neuronal nuclei polyploid? Histochemistry 43, 59–61 (1975)
Bregnard, A., Kuenzle, C.C., Ruch, F.: Cytophotometric and autoradiographic evidence for postnatal DNA synthesis in neurons of the rat cerebral cortex. Exp. Cell Res. 107, 151–157 (1977)
Breindl, M., Gallwitz, D.: On the translational control of histone synthesis. Quantitation of biologically active histone mRNA from synchronized HeLa cells and its translation in different cell-free systems. Eur J. Biochem. 45, 91–97 (1974)
Burdman, J.A.: Incorporation in vivo of radioactive leucine into neuronal and glial nuclear proteins of rat brain. J. Neurochem. 17, 1555–1562 (1970)
Felsenfeld, G.: Chromatin. Nature 271, 115–122 (1978)
Fukuei, K., Yakura, K., Tanifuji, S.: Non-coordinated histone synthesis with DNA replication and close temporal association of ribosomal proteins and rRNA syntheses in germinating Vicia faba embryos. Biochim. Biophys. Acta 518, 390–400 (1978)
Gallwitz, D., Mueller, G.C.: Histone synthesis in vitro on HeLa Cell microsomes. The nature of the coupling to deoxyribonucleic acid synthesis. J. Biol. Chem. 244, 5947–5952 (1969)
Grellet, F., Delseny, M., Guitton, Y.: Histone content of germinating pea embryo chromatin decreases as DNA replicates. Nature 267, 724–726 (1977)
Hübscher, U., Kuenzle, C.C., Spadari, S.: Variation of DNA polymerases-α,-β, and γ during perinatal tissue growth and differentiation. Nucleic Acids Res. 4, 2917–2929 (1977)
Jackson, V., Granner, D.K., Chalkley R.: Deposition of histones onto replicating chromosomes. Proc. Natl. Acad. Sci. USA 72, 4440–4444 (1975)
Jackson, V., Granner, D., Chalkley R.: Deposition of histone onto the replicating chromosome: Newly synthesized histone is not found near the replication fork. Proc. Natl. Acad. Sci. USA 73, 2266–2269 (1976)
Jacobson, M.: Developmental neurobiology, p. 1–74, New York: Holt, Rinehard & Winston 1970
Kuenzle, C.C., Knüsel, A., Schümperli, D.: Isolation of neuronal nuclei from rat brain cortex, rat cerebellum, and pigeon forebrain. Methods Cell Biol. 15, 89–96 (1977)
Kuenzle, C.C., Bregnard, A., Hübscher U., Ruch, F.: Extra DNA in forebrain cortical neurons. Exp. Cell Res. 113, 151–160 (1978)
Leemann, U., Ruch, F.: Cytofluorometric determination of basic and total proteins with sulfaflavine. J. Histochem. Cytochem. 20, 659–671 (1972)
Leemann, U., Weiss, S., Schmutz, E.: A centrifugation technique for cytochemical preparations. J. Histochem. Cytochem. 19, 758–760 (1971)
Medvedev, Zh.A., Medvedeva, M.N., Huschtscha, L.I.: Age changes of the pattern of F1 histone subfractions on rat liver and spleen chromatin. Gerontology 23, 334–341 (1977)
Medvedev, Zh.A., Medvedeva, M.N., Robson, L.: Tissue specificity and age changes of the pattern of the H1 group of histones in chromatin from mouse tissues. Gerontology 24, 286–292 (1978)
Nadeau, P., Oliver, D.R., Chalkley, R.: Effect of inhibition of DNA synthesis on histone synthesis and deposition. Biochemistry 17, 4885–4893 (1978)
Panyim, S., Chalkley, R.: High resolution acrylamide gel electrophoresis of histones. Arch. Biochem. Biophys. 130, 337–346 (1969a)
Panyim, S., Chalkley, R.: A new histone found in mammalian tissues with little cell division. Biochem. Biophys. Res. Commun. 37, 1042–1049 (1969b)
Prescott D.M.: The syntheses of total macronuclear protein, histone, and DNA during the cell cycle in Euplotes eurystomus. J. Cell Biol. 31, 1–9 (1966)
Robbins, E., Borun, T.W.: The cytoplasmic synthesis of histones in HeLa cells and its temporal relationship to DNA replication. Proc. Natl. Acad. Sci. USA 57, 409–416 (1967)
Ruch, R., Leemann, U.: Cytofluorometry. In: Micromethods in molecular biology. V. Neuhoff (ed.), pp. 329–346. Berlin, Heidelberg, New York: Springer 1973
Seale, R.L.: Temporal relationship of chromatin protein synthesis, DNA synthesis, and assembly of deoxyribonucleoprotein. Proc. Natl. Acad. Sci. USA 73, 2270–2274 (1976)
Sellinger, O.Z., Azcurra, J.M., Johnson, D.E., Ohlsson, W.G., Lodin, Z.: Independence of protein synthesis and drug uptake in nerve cell bodies and glial cells isolated by a new technique. Nature (New Biol.) 230, 253–256 (1971)
Zlatanova, J., Swetly, P.: Uncoupled synthesis of histones and DNA during Friend cell differentiation. Nature 276, 276–277 (1978)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Bregnard, A., Ruch, F., Lutz, H. et al. Histones and DNA increase synchronously in neurons during early postnatal development of the rat forebrain cortex. Histochemistry 61, 271–279 (1979). https://doi.org/10.1007/BF00508448
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00508448