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Radial glia-like cells at the base of the lateral ventricles in adult mice

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Journal of Neurocytology

Abstract

During development radial glia (RG) are neurogenic, provide a substrate for migration, and transform into astrocytes. Cells in the RG lineage are functionally and biochemically heterogeneous in subregions of the brain. In the subventricular zone (SVZ) of the adult, astrocyte-like cells exhibit stem cell properties. During examination of the response of SVZ astrocytes to brain injury in adult mice, we serendipitously found a population of cells in the walls of the ventral lateral ventricle (LV) that were morphologically similar to RG. The cells expressed vimentin, glial fibrillary acidic protein (GFAP), intermediate filament proteins expressed by neural progenitor cells, RG and astrocytes. These RG-like cells had long processes extending ventrally into the nucleus accumbens, ventromedial striatum, ventrolateral septum, and the bed nucleus of the stria terminalis. The RG-like cell processes were associated with a high density of doublecortin-positive cells. Lesioning the cerebral cortex did not change the expression of vimentin and GFAP in RG-like cells, nor did it alter their morphology. To study the ontogeny of these cells, we examined the expression of molecules associated with RG during development: vimentin, astrocyte-specific glutamate transporter (GLAST), and brain lipid-binding protein (BLBP). As expected, vimentin was expressed in RG in the ventral LV embryonically (E16, E19) and during the first postnatal week (P0, P7). At P14, P21, P28 as well as in the adult (8–12 weeks), the ventral portion of the LV retained vimentin immunopositive RG-like cells, whereas RG largely disappeared in the dorsal two-thirds of the LV. GLAST and BLBP were expressed in RG of the ventral LV embryonically and through P7. In contrast to vimentin, at later stages BLBP and GLAST were found in RG-like cell somata but not in their processes. Our results show that cells expressing vimentin and GFAP (in the radial glia-astrocyte lineage) are heterogeneous dorsoventrally in the walls of the LV. The results suggest that not all RG in the ventral LV complete the transformation into astrocytes and that the ventral SVZ may be functionally dissimilar from the rest of the SVZ.

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References

  • ALVAREZ-BUYLLA, A. (1990) Mechanism of neurogenesis in adult avian brain. Experientia 46, 948-955.

    Google Scholar 

  • ALVAREZ-BUYLLA, A., BUSKIRK, D. R. & NOTTEBOHM, F. (1987) Monoclonal antibody reveals radial glia in adult avian brain. Journal of Comparative Neurology 264, 159-170.

    Google Scholar 

  • ALVAREZ-BUYLLA, A. & GARCIA-VERDUGO, J. M. (2002) Neurogenesis in adult subventricular zone. Journal of Neuroscience 22, 629-634.

    Google Scholar 

  • ALVAREZ-BUYLLA, A., THEELEN, M. & NOTTEBOHM, F. (1988) Mapping of radial glia and of a new cell type in adult canary brain. Journal of Neuroscience 8, 2707-2712.

    Google Scholar 

  • BRIGHTMAN, M. W. & PALAY, S. L. (1963) The fine structure of ependyma in the brain of rat. Journal of Cell Biology 19, 415-439.

    Google Scholar 

  • BRUNI, J. E. (1998) Ependymal development, proliferation, and functions: A review. Microscopy Research and Technique 41, 2-13.

    Google Scholar 

  • CAMPBELL, K. & GOTZ, M. (2002) Radial glia: Multipurpose cells for vertebrate brain development. Trends in Neurosciences 25, 235-238.

    Google Scholar 

  • CHANAS-SACRE, G., ROGISTER, B., MOONEN, G. & LEPRINCE, P. (2000a) Radial glia phenotype: Origin, regulation, and transdifferentiation. Journal of Neuroscience Research 61, 357-363.

    Google Scholar 

  • CHANAS-SACRE, G., THIRY, M., PIRARD, S., ROGISTER, B., MOONEN, G., MBEBI, C., VERDIERE-SAHUQUE, M. & LEPRINCE, P. (2000b) A 295-kDA intermediate filament-associated protein in radial glia and developing muscle cells in vivo and in vitro. Developmental Dynamics 219, 514-525.

    Google Scholar 

  • DOETSCH, F., CAILLE, I., LIM, D. A., GARCIA-VERDUGO, J. M. & ALVAREZ-BUYLLA, A. (1999a) Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell 97, 703-716.

    Google Scholar 

  • DOETSCH, F., GARCIA-VERDUGO, J. M. & ALVAREZ-BUYLLA, A. (1997) Cellular composition and three-dimensional organization of the subventricular germinal zone in the adult mammalian brain. Journal of Neuroscience 17, 5046-5061.

    Google Scholar 

  • DOETSCH, F., GARCIA-VERDUGO, J. M. & ALVAREZBUYLLA, A. (1999b) Regeneration of a germinal layer in the adult mammalian brain. Proceedings of the National Academy of Sciences of the United States of America 96, 11619-11624.

    Google Scholar 

  • DOETSCH, F., PETREANU, L., CAILLE, I., GARCIAVERDUGO, J. M. & ALVAREZ-BUYLLA, A. (2002) EGF converts transit-amplifying neurogenic precursors in the adult brain into multipotent stem cells. Neuron 36, 1021-1034.

    Google Scholar 

  • FLAMENT-DURAND, J. & BRION, J. P. (1985) Tanycytes: Morphology and functions: A review. International Review of Cytology 96, 121-155.

    Google Scholar 

  • FONT, E., DESFILIS, E., PEREZ-CANELLAS, M. M. & GARCIA-VERDUGO, J. M. (2001) Neurogenesis and neuronal regeneration in the adult reptilian brain. Brain, Behavior and Evolution 58, 276-295.

    Google Scholar 

  • FRANCIS, F., KOULAKOFF, A., BOUCHER, D., CHAFEY, P., SCHAAR, B., VINET, M. C., FRIOCOURT, G., MCDONNELL, N., REINER, O., KAHN, A., MCCONNELL, S. K., BERWALD-NETTER, Y., DENOULET, P. & CHELLY, J. (1999) Doublecortin is a developmentally regulated, microtubule-associated protein expressed in migrating and differentiating neurons. Neuron 23, 247-256.

    Google Scholar 

  • GLEESON, J. G., LIN, P. T., FLANAGAN, L. A. & WALSH, C. A. (1999) Doublecortin is a microtubule-associated protein and is expressed widely by migrating neurons. Neuron 23, 257-271.

    Google Scholar 

  • GOINGS, G., SAHNI, V. & SZELE, F. (2004) Migration patterns of subventricular zone cells in adult mice change after cerebral cortex injury. Brain Research 996, 213-226.

    Google Scholar 

  • GOINGS, G., WIBISONO, B. & SZELE, F. (2002) Cerebral cortex lesions decrease the number of bromodeoxyuridine-positive subventricular zone cells in mice. Neuroscience Letters 329, 161-164.

    Google Scholar 

  • GOTZ, M., STOYKOVA, A. & GRUSS, P. (1998) Pax6 controls radial glia differentiation in the cerebral cortex. Neuron 21, 1031-1044.

    Google Scholar 

  • GRANGER, B. L. & LAZARIDES, E. (1979) Desmin and vimentin coexist at the periphery of the myofibril Z disc. Cell 18, 1053-1063.

    Google Scholar 

  • HARTFUSS, E., GALLI, R., HEINS, N. & GOTZ, M. (2001) Characterization of CNS precursor subtypes and radial glia. Developmental Biology 229, 15-30.

    Google Scholar 

  • HUNTER, K. E. & HATTEN, M. E. (1995) Radial glial cell transformation to astrocytes is bidirectional: Regulation by a diffusible factor in embryonic forebrain. Proceedings of the National Academy of Sciences of the United States of America 92, 2061-2065.

    Google Scholar 

  • JANKOVSKI, A. & SOTELO, C. (1996) Subventricular zone-olfactory bulb migratory pathway in the adult mouse: Cellular composition and specificity as determined by heterochronic and heterotopic transplantation. Journal of Comparative Neurology 371, 376-396.

    Google Scholar 

  • KAWAGUCHI, A., MIYATA, T., SAWAMOTO, K., TAKASHITA, N., MURAYAMA, A., AKAMATSU, W., OGAWA, M., OKABE, M., TANO, Y., GOLDMAN, S. A. & OKANO, H. (2001) Nestin-EGFP transgenic mice: Visualization of the self-renewal and multipotency of CNS stem cells. Molecular and Cellular Neurosciences 17, 259-273.

    Google Scholar 

  • KINTNER, C. (2002) Neurogenesis in embryos and in adult neural stem cells. Journal of Neuroscience 22, 639-643.

    Google Scholar 

  • LAZZARI, M. & FRANCESCHINI, V. (2001) Glial fibrillary acidic protein and vimentin immunoreactivity of astroglial cells in the central nervous system of adult Podarcis sicula (Squamata, Lacertidae). Journal of Anatomy 198, 67-75.

    Google Scholar 

  • LEAVITT, B. R., HERNIT-GRANT, C. S. & MACKLIS, J. D. (1999) Mature astrocytes transform into transitional radial glia within adult mouse neocortex that supports directed migration of transplanted immature neurons. Experimental Neurology 157, 43-57.

    Google Scholar 

  • LENDAHL, U., ZIMMERMAN, L. B. & MCKAY, R. D. (1990) CNS stem cells express a new class of intermediate filament protein. Cell 60, 585-595.

    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. Journal of Comparative Neurology 193, 815-840.

    Google Scholar 

  • LOIS, C. & ALVAREZ-BUYLLA, A. (1993) Proliferating subventricular zone cells in the adult mammalian forebrain can differentiate into neurons and glia. Proceedings of the National Academy of Sciences of the United States of America 90, 2074-2077.

    Google Scholar 

  • LOIS, C. & ALVAREZ-BUYLLA, A. (1994) Long-distance neuronal migration in the adult mammalian brain. Science 264, 1145-1148.

    Google Scholar 

  • LOIS, C., GARCIA-VERDUGO, J. M. & ALVAREZBUYLLA, A. (1996) Chain migration of neuronal precursors. Science 271, 978-981.

    Google Scholar 

  • LUSKIN, M. B. (1993) Restricted proliferation and migration of postnatally generated neurons derived from the forebrain subventricular zone. Neuron 11, 173-189.

    Google Scholar 

  • MALATESTA, P., HARTFUSS, E. & GOTZ, M. (2000) Isolation of radial glial cells by fluorescent-activated cell sorting reveals a neuronal lineage. Development 127, 5253-5263.

    Google Scholar 

  • MARTINEZ, G., CARNAZZA, M. L., DI GIACOMO, C., SORRENTI, V., AVITABILE, M. & VANELLA, A. (1998) GFAP, S-100 and vimentin proteins in rat after cerebral post-ischemic reperfusion. International Journal of Developmental Neuroscience 16, 519-526.

    Google Scholar 

  • MCDERMOTT, K. W. & LANTOS, P. L. (1989) The distribution of glial fibrillary acidic protein and vimentin in postnatal marmoset (Callithrix jacchus) brain. Brain Research. Developmental Brain Research 45, 169-177.

    Google Scholar 

  • MISSION, J. P., TAKAHASHI, T. & CAVINESS, V. S., JR. (1991) Ontogeny of radial and other astroglial cells in murine cerebral cortex. Glia 4, 138-148.

    Google Scholar 

  • MITRO, A. & PALKOVITS, M. (1981) Morphology of the rat brain ventricles, ependyma, and periventricular structures. Bibliotheca Anatomica 1-110.

  • MORI, K., IKEDA, J. & HAYAISHI, O. (1990) Monoclonal antibody R2D5 reveals midsagittal radial glial system in postnatally developing and adult brainstem. Proceedings of the National Academy of Sciences of the United States of America 87, 5489-5493.

    Google Scholar 

  • MORSHEAD, C. M. & VAN DER KOOY, D. (1992) Postmitotic death is the fate of constitutively proliferating cells in the subependymal layer of the adult mouse brain. Journal of Neuroscience 12, 249-256.

    Google Scholar 

  • NACHER, J., CRESPO, C. & MCEWEN, B. S. (2001) Doublecortin expression in the adult rat telencephalon. European Journal of Neuroscience 14, 629-644.

    Google Scholar 

  • NAUJOKS-MANTEUFFEL, C. & ROTH, G. (1989) Astroglial cells in a salamander brain (Salamandra salamandra) as compared to mammals: A glial fibrillary acidic protein immunohistochemistry study. Brain Research 487, 397-401.

    Google Scholar 

  • NOCTOR, S. C., FLINT, A. C., WEISSMAN, T. A., DAMMERMAN, R. S. & KRIEGSTEIN, A. R. (2001) Neurons derived from radial glial cells establish radial units in neocortex. Nature 409, 714-720.

    Google Scholar 

  • NOCTOR, S. C., FLINT, A. C., WEISSMAN, T. A., WONG, W. S., CLINTON, B. K. & KRIEGSTEIN, A. R. (2002) Dividing precursor cells of the embryonic cortical ventricular zone have morphological and molecular characteristics of radial glia. Journal of Neuroscience 22, 3161-3173.

    Google Scholar 

  • PAXINOS, G. & FRANKLIN, K. B. J. (2001) The Mouse Brain in Stereotaxic Coordinates. San Diego: Academic Press.

    Google Scholar 

  • PIXLEY, S. K. & DE VELLIS, J. (1984) Transition between immature radial glia and mature astrocytes studied with a monoclonal antibody to vimentin. Brain Research 317, 201-209.

    Google Scholar 

  • PRIVAT, A. & LEBLOND, C. P. (1972) The subependymal layer and neighboring region in the brain of the young rat. Journal of Comparative Neurology 146, 277-302.

    Google Scholar 

  • RAKIC, P. (1978) Neuronal migration and contact guidance in the primate telencephalon. Postgraduate Medical Journal 54(Suppl 1), 25-40.

    Google Scholar 

  • REICHENBACH, A. (1990) Radial glial cells are present in the velum medullare of adult monkeys. Journal fur Hirnforschung 31, 269-271.

    Google Scholar 

  • REYNOLDS, B. A. & WEISS, S. (1992) Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system [see comments]. Science 255, 1707-1710.

    Google Scholar 

  • RICHARDS, L. J., KILPATRICK, T. J. & BARTLETT, P. F. (1992) De novo generation of neuronal cells from the adult mouse brain. Proceedings of the National Academy of Sciences of the United States of America 89, 8591-8595.

    Google Scholar 

  • ROUSSELOT, P., HEINTZ, N. & NOTTEBOHM, F. (1997) Expression of brain lipid binding protein in the brain of the adult canary and its implications for adult neurogenesis. Journal of Comparative Neurology 385, 415-426.

    Google Scholar 

  • SCHMECHEL, D. E. & RAKIC, P. (1979) A Golgi study of radial glial cells in developing monkey telencephalon: Morphogenesis and transformation into astrocytes. Anatomy and Embryology 156, 115-152.

    Google Scholar 

  • SHIBATA, T., YAMADA, K., WATANABE, M., IKENAKA, K., WADA, K., TANAKA, K. & INOUE, Y. (1997) Glutamate transporter GLAST is expressed in the radial glia-astrocyte lineage of developing mouse spinal cord. Journal of Neuroscience 17, 9212-9219.

    Google Scholar 

  • SMART, I. (1961) The subependymal layer of the mousebrain and its cell production as shown by radioautography after thymidine-H3 injection. J. Comp. Neurol 116, 325-338.

    Google Scholar 

  • STEVENSON, J. A. & YOON, M. G. (1982) Morphology of radial glia, ependymal cells, and periventricular neurons in the optic tectum of goldfish (Carassius auratus). Journal of Comparative Neurology 205, 128-138.

    Google Scholar 

  • SZELE, F. & SZUCHET, S. (2003) Cells lining the ventricular system: Evolving concepts underlying developmental events in the embryo and adult. Advances in Molecular and Cell Biology 31, 127-147.

    Google Scholar 

  • SZELE, F. G., ALEXANDER, C. & CHESSELET, M. F. (1995) Expression of molecules associated with neuronal plasticity in the striatum after aspiration and thermocoagulatory lesions of the cerebral cortex in adult rats. Journal of Neuroscience 15, 4429-4448.

    Google Scholar 

  • SZELE, F. G. & CHESSELET, M. F. (1996) Cortical lesions induce an increase in cell number and PSA-NCAM expression in the subventricular zone of adult rats. Journal of Comparative Neurology 368, 439-454.

    Google Scholar 

  • THOMAS, L. B., GATES, M. A. & STEINDLER, D. A. (1996) Young neurons from theadult subependymal zone proliferate and migrate along an astrocyte, extracellular matrix-rich pathway. Glia 17, 1-14.

    Google Scholar 

  • TOMIZAWA, K., INOUE, Y. & NAKAYASU, H. (2000) A monoclonal antibody stains radial glia in the adult zebrafish (Danio rerio) CNS. Journal of Neurocytology 29, 119-128.

    Google Scholar 

  • TRAMONTIN, A. D., GARCIA-VERDUGO, J. M., LIM, D. A. & ALVAREZ-BUYLLA, A. (2003) Postnatal development of radial glia and the ventricular zone (VZ): A continuum of the neural stem cell compartment. Cerebral Cortex 13, 580-587.

    Google Scholar 

  • YAMAGUCHI, M., SAITO, H., SUZUKI, M. & MORI, K. (2000) Visualization of neurogenesis in the central nervous system using nestin promoter-GFP transgenic mice [In Process Citation]. Neuroreport 11, 1991-1996.

    Google Scholar 

  • YUASA, S. (1996) Bergmann glial development in the mouse cerebellum as revealed by tenascin expression. Anatomy and Embryology 194, 223-234.

    Google Scholar 

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  1. CMIER Neurobiology Program, Children's Memorial Hospital, Department of Pediatrics, Feinberg School of Medicine, Northwestern University, 2430 N. Halsted, No. 209, Chicago, IL, 60614-3394, USA

    Nikki L. Sundholm-Peters, Helen K. C. Yang, Gwendolyn E. Goings, Avery S. Walker & Francis G. Szele

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  1. Nikki L. Sundholm-Peters
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  2. Helen K. C. Yang
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  3. Gwendolyn E. Goings
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  5. Francis G. Szele
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Correspondence to Francis G. Szele.

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Sundholm-Peters, N.L., Yang, H.K.C., Goings, G.E. et al. Radial glia-like cells at the base of the lateral ventricles in adult mice. J Neurocytol 33, 153–164 (2004). https://doi.org/10.1023/B:NEUR.0000029654.70632.3a

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