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Mechanisms of glial-guided neuronal migration in vitro and in vivo

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Summary

Our laboratory has developed an in vitro model system in which glial-guided neuronal migration can be observed in real time. Cerebellar granule neurons migrate on astroglial fibers by apposing their cell soma against the glial arm, forming a specialized migration junction, and extending a motile leading process in the direction of migration. In vitro assays indicate that the neuronal antigen astrotactin functions as a neuron-glia ligand, and is likely to play a role in the movement of neurons along glial fibers. In heterotypic recombinations of neurons and glia from mouse cerebellum and rat hippocampus, neurons migrate on heterotypic glial processes with a cytology, speed and mode of movement identical to that of neuronal migration on homotypic glial fibers, suggesting that glial fibers provide a permissive pathway for neuronal migration in developing brain. In vivo analyses of developing cerebellum demonstrate a close coordination of afferent axon ingrowth relative to target cell migration. These studies indicate that climbing fibers contact immature Purkinje neurons during the migration and settling of Purkinje cells, implicating a role for afferents in the termination of migration.

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References

  1. Abercrombie, M., and Heaysman, J.M., Observations on the social behavior of cells in tissue culture. Exp. Cell Res.6 (1954) 293–306.

    Article  CAS  PubMed  Google Scholar 

  2. Caviness, V.S. Jr, Patterns of cell and fiber distribution in the neocortex of the reeler mutant mouse. J. comp. Neurol.170 (1976) 435–448.

    Article  PubMed  Google Scholar 

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

    Article  Google Scholar 

  4. Caviness, V.S Jr, and Rakic, P., Mechanisms of Cortical Development. A View from Mutations in Mouse. A. Rev. Neurosci1 (1978) 297–326.

    Article  Google Scholar 

  5. Dodd, J., Morton, S.B., Karagorgeos, D., Yamamoto, M., and Jessell, T.M., Spatial regulation of axonal glycoprotein expression on subsets of embryonic spinal neurons. Neuron1 (1988) 105–116.

    Article  CAS  PubMed  Google Scholar 

  6. Eckenhoff, M.F., and Rakic, P., Radial organization of the hippocampal dentate gyrus: a golgi, ultrastructural, and immunocytochemical analysis in the developing rhesus monkey. J. comp. Neur.223 (1984) 1–21.

    Article  CAS  PubMed  Google Scholar 

  7. Edelman, G.D., and Chuong, C.-M., Embryonic to adult conversion of neural cell adhesion molecules in normal and staggerer mutant mice. Proc. natl Acad. Sci. USA79 (1982) 7036–7040.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Edmondson, J.C., and Hatten, M.E., Glial-guided granule neuron migration in vitro: a high-resolution time-lapse video microscopic study. J. Neurosci.7 (1987) 1928–1934.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Edmondson, J.C., Liem, R.K.H., Kuster, J.C., and Hatten, M.E., Astrotactin: anovel neuronal cell surface antigen that mediates neuron-astroglial interactions in cerebellar microcultures. J. Cell Biol.106 (1988) 505–517.

    Article  CAS  PubMed  Google Scholar 

  10. Gasser, U.E., and Hatten, M.E., Neuron-glia interactions of rat hippocampal cells in vitro: glial-guided neuronal migration and neuronal regulation of glial differentiation. J. Neurosci.10 (1990) 1276–1285.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Gasser, U.E., and Hatten, M.E., CNS neurons migrate on astroglial fibers from heterotypic brain regions in vitro. Proc. natl Acad. Sci. USA87 (1990) 4543–4547.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Gregory, W.A., Edmondson, J.C., Hatten, M.E., and Mason, C.A., Cytology and neuron-glia apposition of migrating cerebellar granule cells in vitro. J. Neurosci.8 (1988) 1728–1738.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Hatta, K., Okada, T.S., and Takeichi, M., A monoclonal antibody disrupting calcium dependent cell-cell adhesion of brain tissue. Possible role of its target antigen in animal pattern formation. Proc. natl Acad. Sci. USA82 (1985) 2789–2793.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Hatten, M.E., Neuronal regulation of astroglial morphology and proliferation in vitro. J. Cell Biol.100 (1985) 384–396.

    Article  CAS  PubMed  Google Scholar 

  15. Hatten, M.E., Neuronal inhibition of astroglial cell proliferation is membrane mediated. J. Cell Biol.104 (1987) 1353–1360.

    Article  CAS  PubMed  Google Scholar 

  16. Hatten, M.E., Glial-guided neuronal migration in vitro, pp. 469–489. Eds J.-P. Thiery, B.A. Cunningham and G.M. Edelman. Wiley, New York 1990.

    Google Scholar 

  17. Hatten, M.E. Riding the glial monorail: a common mechanism for glial-guided migration in different regions of the developing brain. Trends Neurosci.13 (1990) 179–187.

    Article  CAS  PubMed  Google Scholar 

  18. Hatten, M.E., Neuronal regulation of astroglial proliferation and differentiation, in: The Assembly of the Nervous System, pp. 151–166. Ed. L.T. Landmesser. Alan R. Liss Inc., New York 1989.

    Google Scholar 

  19. Hatten, M.E., and Liem, R.K.H., Astroglia provide a template for the positioning of developing cerebellar neurons in vitro. J. Cell Biol.90 (1981) 622–630.

    Article  CAS  PubMed  Google Scholar 

  20. Hatten, M.E., Liem, R.K.H., Mason, C.A., Two forms of cerebellar glial cells interact differently with neurons in vitro. J. Cell Biol.98 (1984) 193–204.

    Article  CAS  PubMed  Google Scholar 

  21. Hatten, M.E., Liem, R.K.H., and Mason, C.A., Weaver mouse cerebellar granule neurons fail to migrate on wild-type astroglial processes in vitro. J. Neurosci.9 (1986) 2676–2683.

    Article  Google Scholar 

  22. Inouye, M., and Murakami, U., Temporal and spatial patterns of Purkinje cell formation in the mouse cerebellum. J. comp. Neurol.194 (1980) 499–503.

    Article  CAS  PubMed  Google Scholar 

  23. Issacson, R.L., and Pribram, K.H. (Eds) The Hippocampus, vol. 1, Structure and Development, Plenum, New York 1975.

    Google Scholar 

  24. Jensen, K.F., and Killackey, H.P., Subcortical projections from ectopic neocortical neurons. Proc. natl Acad. Sci. USA81 (1984) 964–968.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Jessell, T.M., Adhesion molecules and the hierarchy of neural development. Neuron1 (1988) 3–13.

    Article  CAS  PubMed  Google Scholar 

  26. Jones, E.G., Valentino, K.L., and Fleshman, J.W. Jr, Adjustment of connectivity in rat neocortex after prenatal destruction of precursor cells of layer II–IV. Dev. Brain Res.2 (1982) 498–500.

    Google Scholar 

  27. Lindner, J., Rathjen, F.G., and Schachner, M., L1 mono- and polyclonal antibodies modify cell migration in early postnatal mouse cerebellum. Nature (Lond.)305 (1983) 427–430.

    Article  CAS  PubMed  Google Scholar 

  28. Mason, C.A., Edmondson, J.C., and Hatten, M.E., The extending astroglial process: development of glial shape, the growing tip and interactions with neurons. J. Neurosci.8 (1988) 3124–3134.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Mason, C.A., Axon development in mouse cerebellum: Embryonic axon forms and expression of synapsin I. Neuroscience19 (1986) 1319–1333.

    Article  CAS  PubMed  Google Scholar 

  30. Mason, C.A., The development of cerebellar mossy fibers and climbing fibers: embryonic and postnatal features, in: New Concepts in Cerebellar Neurobiology, pp. 57–88. Ed J.S. King; for series Neurology and Neurobiology; Eds V. Chan-Palay and S. Palay. A.R. Liss, New York 1987.

    Google Scholar 

  31. Mason, C.A., Afferent climbing fibers interact with target Purkinje cells in embryonic mouse cerebellum. J. comp. Neurol. (1990) in press.

  32. Mason, C.A., and Gregory, E., Postnatal maturation of cerebellar mossy and climbing fibers: Transient expression of dual features on single axons. J. Neurosci.4 (1984) 1715–1735.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Mason, C.A., and Blazeski, R., Climbing fibers contact target Purkinje cells in embryonic mouse cerebellum. Soc. Neurosci Abstr.15 (1989) 959.

    Google Scholar 

  34. Mason, C.A., Christakos, S., and Catalano, S.M., Early climbing fibers interactions with Purkinje cells in postnatal mouse cerebellum. J. comp. Neurol.297 (1990) 77–90.

    Article  CAS  PubMed  Google Scholar 

  35. McConnell, S.K., Fates of visual cortical neurons in the ferret after isochronic and heterochronic transplantation. J. Neurosci.8 (1988) 945–974.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. McConnell, S.K., Development and decision making in the mammalian cerebral cortex. Brain Res. Rev.13 (1988) 1–23.

    Article  Google Scholar 

  37. McGuire, J.C., Greene, L.A., and Furano, A.V., NGF stimulated incorporation of fucose or glucosamine into an external glycoprotein of cultured rat PC 12 pheochromocytoma cells. Cell15 (1978) 357–365.

    Article  CAS  PubMed  Google Scholar 

  38. Miale, I.L., and Sidman, R.L., An autoradiographic analysis of histogenesis in the mouse cerebellum. Exp. Neurol.4 (1961) 277–296.

    Article  CAS  PubMed  Google Scholar 

  39. Misson, J.-P., Edwards, M., Yamamoto, M., and Caviness, V.S. Jr, Identification of radial glial cells within the developing murine central nervous system: studies based upon a new immunohistochemical marker. Dev. Brain Res.44 (1988) 95–108.

    Article  CAS  Google Scholar 

  40. Nowakowski, R., and Rakic, P., The mode of migration of neurons to the hippocampus: A Golgi and electron microscopic analysis in fetal rhesus monkeys. J. Neurocytol.8, (1979) 697–718.

    Article  CAS  PubMed  Google Scholar 

  41. O'Leary, D.D.M., and Terashima, T., Cortical axons branch to multiple subcortical targets by interstitial axon budding: Implications for target recognition and ‘waiting periods’. Neuron1 (1988) 901–910.

    Article  CAS  PubMed  Google Scholar 

  42. Palay, S.L., and Palay, S.F., Cerebellar Cortex, Cytology and Organization. Springer, New York 1974.

    Book  Google Scholar 

  43. Persohn, E., and Schachner, M., Immunoelectron microscopic localization of the neural cell adhesion molecules L1 and N-CAM during postnatal development of the cerebellum. J. Cell Biol.105 (1987) 569–576.

    Article  CAS  PubMed  Google Scholar 

  44. Pinto Lord, M.C., Evrard, P., and Caviness, V.S. Jr, Obstructed neuronal migration along radial fibers in the neocortex of the reeler mouse: a Golgi-EM analysis. Dev. Brain Res.4 (1982) 379–393.

    Article  Google Scholar 

  45. Rakic, P., Neuron-glia relationship during granule cell migration in developing cerebellar cortex. A Golgi and electron microscopic study in Macacus rhesus. J. comp. Neurol.141 (1971) 283–312.

    Article  CAS  PubMed  Google Scholar 

  46. Rakic, P., Mode of cell migration to the superficial layers of foetal monkey neocortex. J. comp. Neurol.145 (1972) 61–84.

    Article  CAS  PubMed  Google Scholar 

  47. Rakic, P., Neuronal migration and contact guidance in primate telencephalon. Postgrad. Med. J.54 (1978) 25–40.

    PubMed  Google Scholar 

  48. Rakic, P., in: The cell in contact: Adhesions and junctions as morphological determinants, pp. 67–91. Eds G. M. Edelman and J.-P. Thiery, Neuroscience Research Foundation, New York 1985.

    Google Scholar 

  49. Rakic, P., Defects of neuronal migration and the pathogenesis of cortical malformations. Eds G.J. Boer, M.G.P. Feenstra, M. Mimiran, D.F. Swaab and F. Van Haaren. Prog. Brain Res.73 (1988) 15–37.

    Article  CAS  PubMed  Google Scholar 

  50. Rakic, P., and Sidman, R.L.,Weaver mutant mouse cerebellum: defective neuronal migration secondary to specific abnormality of Bergmann glia. Proc. natl Acad. Sci. USA70 (1973) 240–244.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Rakic, P., Stensaas, L.J., Sayre, E.P., and Sidman, R.L., Computer-aided three dimensional reconstruction and quantitative analysis of cells from serial electron microscopic montages of fetal monkey brain. Nature250 (1974) 31–34.

    Article  CAS  PubMed  Google Scholar 

  52. Ramon y Cajal, S., Estructura del Asta de Ammon y fascia dentata. An. Soc. Esp. Hist. nat.22 (1893) 53–114.

    Google Scholar 

  53. Rathjen, F., and Schachner, M., Immunocytochemical and biochemical characterization of a new neuronal cell surface component (L1 antigen) which is involved in cell adhesion. EMBO J.3 (1984) 1–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Reinoso, B.S., and O'Leary, D.D.M., Development of visual thalamocortical projections in the fetal rat. Soc. Neurosci. Abstr.154 (1988) 1113.

    Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  56. Shatz, C.J., Chun, J.J.M., and Luskin, M.B., The role of the subplate in the development of the mammalian telencephalon, in: Cerebral Cortex, vol. 7, pp. 35–58. Eds A. Peters and E.G. Jones. Plenum, New York 1988.

    Chapter  Google Scholar 

  57. Sotelo, C., and Changeaux, J.-P., Bergmann fibers and granule cell migration in the cerebellum of homozygous weaver mutant mouse. Brain Res.77 (1984) 484–494.

    Article  Google Scholar 

  58. Sotelo, C., Bourrat, F., and Triller, A., Postnatal development of the inferior olivary complex in the rat. II. Topographic organization of the immature olivo-cerebellar projection. J. comp. Neurol.222 (1984) 177–199.

    Article  CAS  PubMed  Google Scholar 

  59. Stitt, T.N., and Hatten, M.E., Astrotactin is the primary cell adhesion receptor system in granule neuron binding to astroglia. Neuron (1990) submitted.

  60. Stitt, T.N., Mason, C.A., and Hatten, M.E., The expression of astrotactin, a neuron-glia ligand, is developmentally regulated in developing mouse cerebellum. Neuron (1990) submitted.

  61. Thiery, J.-P., Brackenbury, R., Rutishauser, U., and Edelman, G.M., Adhesion among neural cells of the chick embryo. II. Purification and characterization of a cell adhesion molecule from neural retina. J. biol. Chem.252 (1977) 6841–6845.

    Article  CAS  PubMed  Google Scholar 

  62. Tomaselli, J.J., Neugebauer, K.M., Bixby, J., Lilien, J., and Reichardt, L.F., N-Cadherin and integrins: two receptor systems that mediate neuronal process outgrowth on astrocyte surfaces. Neuron1 (1988) 33–43.

    Article  CAS  PubMed  Google Scholar 

  63. Wise, S.P., and Jones, E.G., Developmental studies of thalamocortical and commissural connections in the rat somatic sensory cortex. J. comp. Neurol.178 (1978) 187–208.

    Article  CAS  PubMed  Google Scholar 

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Hatten, M.E., Mason, C.A. Mechanisms of glial-guided neuronal migration in vitro and in vivo. Experientia 46, 907–916 (1990). https://doi.org/10.1007/BF01939383

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