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The carbohydrate epitope 3-fucosyl-N-acetyllactosamine is developmentally regulated in the human cerebellum

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Summary

The carbohydrate epitope 3-fucosyl-N-acetyllactosamine (CD15) is involved, as a constituent of glycoconjugates, in cell-cell interactions and cell sorting during rodent CNS morphogenesis. The present study was designed to test whether CD15 is also involved in the development of the human CNS. Human cerebellar hemispheres and vermes from the 24th week of gestation (wg) to the 26th postnatal month (pnm) and from adults were investigated for CD15 immunoreactivity, using the monoclonal antibody MMA. Our findings establish that the carbohydrate moiety is developmentally regulated in neuronal and glial cells during their differentiation. First, the parallel fibers of granule cells are CD15+ during the epoch of synaptogenesis with Purkinje cell dendrites. Second, a subpopulation of neurons from the dentate nucleus is transiently CD15 from the 32nd wg until the 15th pnm. Third, at the onset of myelination (around the 35th wg), CD15 immunoreactivity is discernible in the cytoplasm of young oligodendrocytes. Immunoreactivity on protoplasmic astrocytes of the inner granular layer and on fibrous astrocytes of the white matter progressively increases during fetal development. In addition, the CD15 epitope is persistently present on Bergmann glial processes and ependymal cells. Within the three subdivisions of the cerebellum, i.e., hemispheres, vermis, and flocculonodular lobe, the CD15 expression follows a different timing of morphogenesis. For example, diminution of immunoreactivity in the parallel fibers occurs first in the phylogenetically older flocculonodular lobe and vermis, and later in the phylogenetically younger hemispheres. This study shows that in the human cerebellum the distribution of CD15 undergoes marked developmental changes. This epitope may also act in cell-to-cell recognition, and perhaps could play a role in controlling CNS development.

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Abbreviations

wg :

week of gestation

pnd :

postnatal day

pnm :

postnatal month

PF :

parallel fibers

LD :

lamina dissecans

DN :

dentate nucleus

NSE :

neuron-specific enolase

GFAP :

glial fibrillary acidic protein

NF :

neurofilament protein

References

  • Abo T, Balch CM (1981) A differentiation antigen of human NK and K cells identified by a monoclonal antibody (HNK-1). J Immunol 127:1024–1029

    Google Scholar 

  • Altman J (1969) Autoradiographic and histological studies of postnatal neurogenesis. III. Dating the time of production and onset of differentiation of cerebellar microneurons in rats. J Comp Neurol 136:269–294

    Google Scholar 

  • Andrews PW, Gönczöl E, Fenderson BA, Holmes EH, O'Malley G, Hakomori S-i, Plotkin S (1989) Human cytomegalovirus induces stage-specific embryonic antigen 1 in differentiating human teratocarcinoma cells and fibroblasts. J Exp Med 169:1347–1359

    Google Scholar 

  • Bartsch D, Mai J (1989) The distribution of 3-fucosyl-N-acetyllactosamine in the mouse brain. Neuroanatomy and Neurobiology Symposium, Nancy. Bulletin de l'Association des Anatomists, pp 8–9

  • Bell JE, Sandison A, Boddy J, Franks AJ, Batcup G, Calvert R, Gordon A (1989) Development of the cerebellum with particular reference to cellular differentiation in the external granular layer. Early Hum Dev 19:199–211

    Google Scholar 

  • Berliner K (1905) Beiträge zur Histologie und Entwicklungsgeschichte des Kleinhirns, nebst Bemerkungen über die Entwicklung der Funktionstüchtigkeit desselben. Arch Mikrosk Anat 66:220–269

    Google Scholar 

  • Bird JM, Kimber SJ (1984) Oligosaccharides containing fucose-linked α(1 → 3) and α(1 → 4) to N-acetylglucosamine cause decompactation of mouse morulae. Dev Biol 104:449–460

    Google Scholar 

  • Bourrillon R, Aubery M (1989) Cell surface glycoproteins in embryonic development. Int Rev Cytol 116:257–338

    Google Scholar 

  • Brody BA, Kinney HC, Kloman AS, Gilles FH (1987) Sequence of central nervous system myelination in human infancy. I. An autopsy study of myelination. J Neuropathol Exp Neurol 46:283–301

    Google Scholar 

  • Edelman GE, Crossin KL (1991) Cell adhesion molecules: implications for a molecular histology. Annu Rev Biochem 60:155–190

    Google Scholar 

  • Ellis RS (1920) Norms for some structural changes in the human cerebellum from birth to old age. J Comp Neurol 32:1–35

    Google Scholar 

  • Fenderson BA, Zehavi U, Hakomori S-i (1984) A multivalent lacto-N-fucopentaose III-lysyllysine conjugate decompacts preimplantation mouse embryos, while the free oligosaccharide is ineffective. J Exp Med 160:1591–1596

    Google Scholar 

  • Feizi T (1985) Demonstration by monoclonal antibodies that carbohydrate structures of glycoproteins and glycolipids are oncodevelopmental antigens. Nature 314:53–57

    Google Scholar 

  • Fix JD, Treff WM (1970) Bauprinzipien der phylogenetischen Entwicklung der Kleinhirnkerne bei den Primaten. Acta Anat 76:337–351

    Google Scholar 

  • Fox N, Damjanov I, Knowels BB, Solter D (1983) Immunohistochemical localization of the mouse stage-specific embryonic antigen 1 in human tissues and tumors. Cancer Res 43:669–678

    Google Scholar 

  • Friede RL (1973) Dating the development of human cerebellum. Acta Neuropathol (Berl) 23:48–58

    Google Scholar 

  • Friede RL (1989) Developmental neuropathology. 2nd edn. Springer, Berlin

    Google Scholar 

  • Furley AJ, Morton SB, Manalo D, Karagogeos D, Dodd J, Jessell TM (1990) The axonal glycoprotein TAG-1 is an immunoglobulin superfamily member with neurite outgrowth-promoting activity. Cell 61:157–170

    Google Scholar 

  • Gocht A, Löhler J (1990) Changes in glial cell markers in recent and old demyelinated lesions in central pontine myelinolysis. Acta Neuropathol 80:46–58

    Google Scholar 

  • Gooi HC, Feizi T, Kapadia A, Knowels BB, Solter D, Evans MJ (1981) Stage-specific embryonic antigen involves α 1 → 3 fucosylated type 2 blood group chains. Nature 292:156–158

    Google Scholar 

  • Graham RC, Karnovsky MJ (1966) The early stages of absorption of injected horseradish peroxidase in the proximal tubules of mouse kidney. Ultrastructural cytochemistry by a new technique. J Histochem Cytochem 14:291–298

    Google Scholar 

  • Gudovic R, Marinkovic R, Aleksic S (1987) The development of the dentate nucleus in man. Anat Anz 163:233–238

    Google Scholar 

  • Hakomori S-i (1986) Glycosphingolipids. Sci Am 254:32–41

    Google Scholar 

  • Hallgren P, Lundblad A (1977) Structural analysis of nine oligosaccharides isolated from the urine of a blood group O, non-secretor, woman during pregnancy and lactation. J Biol Chem 252:1014–1022

    Google Scholar 

  • Hanjan SNS, Kearney JF, Cooper MD (1982) A monoclonal antibody (MMA) that identifies a differentiation antigen on human myelomonocytic cells. Clin Immunol Immunopathol 23:172–188

    Google Scholar 

  • Hansson GC, Karlsson K-A, Larson G, McKibbin JM, Blaszczyk M, Herlyn M, Steplewski Z, Koprowski H (1983) Mouse monoclonal antibodies against human cancer cell lines with specificities for blood group and related antigens. J Biol Chem 258:4091–4097

    Google Scholar 

  • Hirano A (1983) The normal and aberrant development of synaptic structures between parallel fibers and Purkinje cell dendritic spines. J Neural Transm [Suppl 18]: 1–8

  • Hochstetter F (1929) Die Entwicklung des Mittel- und Rautenhirns. In: Beiträge zur Entwicklungsgeschichte des menschlichen Gehirns, 2. Teil. Deuticke, Wien Leipzig, pp 82–200

    Google Scholar 

  • Hsu SM, Raine L, Fanger H (1981) Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques. A comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem 9:577–580

    Google Scholar 

  • Itzkowitz SH, Yuan M, Fukushi Y, Palekar A, Phelps PC, Shamsuddin AM, Trump BF, Hakomori S-i, Kim YS (1986) Lewisx and sialylated Lewisx-related antigen expression in human malignant and nonmalignant colonic tissues. Cancer Res 46:2627–2632

    Google Scholar 

  • Jakob A (1928) Das Kleinhirn. In: v. Möllendorff W (ed) Handbuch der mikroskopischen Anatomie des Menschen, vol 4. Springer, Berlin

    Google Scholar 

  • Jansen J (1972) Features of cerebellar morphology and organization. Acta Neurol Scand [Suppl 51]: 197–217

  • Jansen J, Brodal A (1958) Das Kleinhirn. In: v. Möllendorff W, Bargmann W (eds) Handbuch der mikroskopischen Anatomie des Menschen, vol 4. Springer, Berlin Heidelberg

    Google Scholar 

  • Jessell TM (1988) Adhesion molecules and the hierarchy of neural development. Neuron 1:3–13

    Google Scholar 

  • Jork R, Smalla K-H, Karsten U, Grecksch G, Rüthrich H-L, Matthies H (1991) Monoclonal antibody specific for histo-blood group antigens H (types 2 and 4) interferes with long-term memory formation in rats. Neurosci Res Commun 8:21–27

    Google Scholar 

  • Kannagi R, Nudelman E, Levery SB, Hakomori S-i (1982) A series of human erythrocyte glycosphingolipids reacting to the monoclonal antibody directed to a developmentally regulated antigen, SSEA-1. J Biol Chem 257:14865–14874

    Google Scholar 

  • Kerr MA, McCarthy NC (1985) A carbohydrate differentiation antigen of granulocytes, brain and many tumours. Biochem Soc Trans 13:424–426

    Google Scholar 

  • Kobata A, Ginsburg V (1969) Oligosaccharides of human milk. II. Isolation and characterization of a new pentasaccharide, lacto-N-fucopentaose III. J Biol Chem 244:5496–5502

    Google Scholar 

  • Kornguth SE, Anderson JW, Scott G (1967) Observations on the ultrastructure of the developing cerebellum of the Macaca mulatta. J Comp Neurol 130:1–24

    Google Scholar 

  • Kumpulainen T, Nyström SHM (1981) Immunohistochemical localization of carbonic anhydrase isoenzyme C in human brain. Brain Res 220:220–225

    Google Scholar 

  • Lagenaur C, Schachner M, Solter D, Knowels B (1982) Monoclonal antibody against SSEA-1 is specific for a subpopulation of astrocytes in mouse cerebellum. Neurosci Lett 31:181–184

    Google Scholar 

  • Larsen E, Palabrica T, Sajer S, Gilbert GE, Wagner DD, Furie BC, Furie B (1990) PADGEM-dependent adhesion of platelets to monocytes and neutrophils is mediated by a lineage-specific carbohydrate, LNF III (CD15). Cell 63:467–474

    Google Scholar 

  • Linnemann D, Bock E (1989) Cell adhesion molecules in neural development. Dev Neurosci 11:149–173

    Google Scholar 

  • Lloyd KO, Kabat EA (1968) Immunochemical studies on blood groups, XLI. Proposed structures for the carbohydrate portions of blood group A, B, H, Lewisa and Lewisb substances. Proc Natl Acad Sci USA 61:1470–1477

    Google Scholar 

  • Loeser JD, Lernire RJ, Alvord EC (1972) The development of the folia in the human cerebellar vermis. Anat Rec 173:109–114

    Google Scholar 

  • Mai JK, Reifenberger G (1988) Distribution of the carbohydrate epitope 3-fucosyl-N-acetyllactosamine (FAL) in the adult human brain. J Chem Neuroanat 1:255–285

    Google Scholar 

  • Mann PL (1988) Membrane oligosaccharides: structure and function during differentiation. Int Rev Cytol 112:67–96

    Google Scholar 

  • McCarthy NC, Simpson JRM, Coghill G, Kerr MA (1985) Expression in normal adult, fetal, and neoplastic tissues of a carbohydrate differentiation antigen recognised by antigranulocyte mouse monoclonal antibodies. J Clin Pathol 38:521–529

    Google Scholar 

  • Mihajlovic P, Zecevic N (1986) Development of the human dentate nucleus. Human Neurobiol 5:189–197

    Google Scholar 

  • Murofushi K (1974) Normalentwicklung und Dysgenesien von Dentatum und Oliva inferior. Acta Neuropathol (Berl) 27:317–328

    Google Scholar 

  • Niedieck B, Löhler J (1987) Expression of 3-fucosyl-N-acetyllactosamine on glia cells and its putative role in cell adhesion. Acta Neuropathol (Berl) 75:173–184

    Google Scholar 

  • Nudelman E, Hakomori S-i, Knowels BB, Solter D, Nowinski RC, Tam MR, Young WW (1980) Monoclonal antibody directed to the stage-specific embryonic antigen (SSEA-1) reacts with a branched glycosphingolipid similar in structure to Ii antigen. Biochem Biophys Res Commun 97:443–451

    Google Scholar 

  • Palay SL, Chan-Palay V (1974) Cerebellar cortex. Cytology and organization. Springer, Berlin

    Google Scholar 

  • Pelc S, Fondu P, Gompel C (1986) Immunohistochemical distribution of glial fibrillary acidic protein, neurofilament polypeptides and neuronal specific enolase in the human cerebellum. J Neurol Sci 73:289–297

    Google Scholar 

  • Perentes E, Rubinstein LJ (1985) Immunohistochemical recognition of human nerve sheath tumors by anti-Leu 7 (HNK-1) monoclonal antibody. Acta Neuropathol (Berl) 68:319–324

    Google Scholar 

  • Rademacher TW, Parekh RB, Dwek RA (1988) Glycobiology. Ann Rev Biochem 57:785–838

    Google Scholar 

  • Rakic P (1971) Neuron-glia relationship during granule cell migration in developing cerebellar cortex. A Golgi and electronmicroscopic study in Macacus rhesus. J Comp Neurol 141:283–312

    Google Scholar 

  • Rakic P (1972) Extrinsic cytological determinants of basket and stellate cell dendritic pattern in the cerebellar molecular layer. J Comp Neurol 146:335–354

    Google Scholar 

  • Rakic P (1973) Kinetics of proliferation and latency between final cell division and onset of differentiation of cerebellar stellate and basket neurons. J Comp Neurol 147:523–546

    Google Scholar 

  • Rakic P, Sidman RL (1970) Histogenesis of cortical layers in human cerebellum, particularly the lamina dissecans. J Comp Neurol 139:473–500

    Google Scholar 

  • Reifenberger G, Mai JK, Krajewski S, Wechsler W (1987) Distribution of anti-Leu-7, anti-Leu-11a and anti-Leu-M1 immunoreactivity in the brain of the adult rat. Cell Tissue Res 248:305–313

    Google Scholar 

  • Rutishauser U, Jessell TM (1988) Cell adhesion molecules in vertebrate neural development. Physiol Rev 68:819–857

    Google Scholar 

  • Schuller-Petrovic S, Gebhart W, Lassmann H, Rumpold H, Kraft D (1983) A shared antigenic determinant between natural killer cells and nervous tissue. Nature 306:179–181

    Google Scholar 

  • Schwarting GA, Yamamoto M (1988) Expression of glycoconjugates during development of the vertebrate nervous system. Bio Essay 9:19–23

    Google Scholar 

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

    Google Scholar 

  • Sidman RL, Rakic P (1982) Development of the human central nervous system. In: Haymaker W, Adams RD (eds) Histology and histopathology of the nervous system. Thomas, Springfield, pp 3–145

    Google Scholar 

  • Skubitz KM, August JT (1985) Characterization of cell surface glycoproteins recognized by the granulocyte-specific monoclonal antibody, AHN-1. Arch Biochem Biophys 238:263–271

    Google Scholar 

  • Skubitz K, Balke J, Ball E, Bridges R, Buescher ES, Campos L, Harvath L, Kerr M, Kniep B, Spitalnik P, Spitalnik S, Skubitz A, Thompson J, Wick M, Williams L (1989) Report on the CDI5 cluster workshop. In: Knapp W (ed) Leucocyte typing IV. White cell differentiation antigens. Oxford University Press, Oxford, pp 800–805

    Google Scholar 

  • Solter D, Knowles BB (1978) Monoclonal antibody defining a stage-specific mouse embryonic antigen (SSEA-1). Proc Natl Acad Sci USA 75:5565–5569

    Google Scholar 

  • Urdal DL, Brentnall TA, Bernstein ID, Hakomori S (1983) A granulocyte reactive monoclonal antibody, 1G10, identifies the Galβ1–4(Fucα1–3)GlcNAc (X determinant) expressed in HL-60 cells on both glycolipid and glycoprotein molecules. Blood 62:1022–1026

    Google Scholar 

  • Yamaguchi K, Goto N, Yamamoto TY (1989) Development of human cerebellar nuclei. Morphometric study. Acta Anat 136:61–68

    Google Scholar 

  • Yamamoto M, Boyer AM, Schwarting GA (1985) Fucose-containing glycolipids are stage- and region-specific antigens in developing embryonic brain of rodents. Proc Natl Acad Sci USA 82:3045–3049

    Google Scholar 

  • Zecevic N, Rakic P (1976) Differentiation of Purkinje cells and their relationship to other components of developing cerebellar cortex in man. J Comp Neurol 167:27–48

    Google Scholar 

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Gocht, A., Zeunert, G., Laas, R. et al. The carbohydrate epitope 3-fucosyl-N-acetyllactosamine is developmentally regulated in the human cerebellum. Anat Embryol 186, 543–556 (1992). https://doi.org/10.1007/BF00186977

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