Influence of Radial Glia and Cajal-Retzius Cells in Neuronal Migration

  • Marcin Gierdalski
  • Sharon L. Juliano
Part of the Results and Problems in Cell Differentiation book series (RESULTS, volume 39)


Normal development of cerebral cortex depends on proper sequential genesis of cortical neurons and glia. Disruption of corticogenesis in ferret by short-term arresting of cell division using injections of methylazoxy methanol (MAM) leads to a specific constellation of effects, including disruption and early differentiation of radial glia into astrocytes and disorganization of reelin-containing Cajal-Retzius cells. We hypothesize that early interference of normal cortical development removes a factor instrumental in maintaining radial glia in their normal elongated shape. In support of this idea, coculture of MAM-treated slices with normal cortical plate restores radial glia and Cajal-Retzius cells to their normal positions. Recently, we found that conditioned medium obtained from normal organotypic cultures returned radial glia toward their normal morphology only in a fraction of 30–50 kDa molecular weight (MW). To assess whether restoring this factor would also improve effective migration into the cortical plate of E24 MAM-treated animals, we conducted experiments using cocultures of normal cortical plate with organotypic cultures of MAM-treated cortex, which received prior BrdU injections. In both the normal and E24 MAM-treated/normal cortical plate coculture, a greater percentage of BrdU positive cells migrated effectively into the cortical plate. We suggest that early interruption of cell division eliminates a population of cells and a factor important for maintaining proper cortical development, specifically providing cues maintaining elongation of radial glia.


Ventricular Zone Radial Glia BrdU Positive Cell Organotypic Culture Cortical Plate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Allendoerfer KL, Shatz CJ (1994) The subplate, a transient neocortical structure: its role in the development of connections between thalamus and cortex. Annu Rev Neurosci 17:185–218PubMedCrossRefGoogle Scholar
  2. Bentivoglio M, Mazzarello P (1999) The history of radial glia. Brain Res Bull 49:305–315PubMedCrossRefGoogle Scholar
  3. Berry M, Rogers AW (1965) The migration of neuroblasts in the developing cerebral cortex. J Anat 99:691–709PubMedGoogle Scholar
  4. Caviness J, Sidman VS, Sidman RL (1973) Time of origin of corresponding cell classes in the cerebral cortex of normal and reeler mutant mice: an autoradiographic analysis. J Comp Neurol 148:141–152PubMedCrossRefGoogle Scholar
  5. Gilmore EC, Herrup K (2000) Cortical development: receiving reelin. Curr Biol 10(4):R162-R166PubMedCrossRefGoogle Scholar
  6. Gilmore EC, Ohshima T, Goffinet AM, Kulkarni AB, Herrup K (1998) Cyclin-dependent kinase 5-deficient mice demonstrate novel developmental arrest in cerebral cortex. J Neurosci 18:6370–6377PubMedGoogle Scholar
  7. Gleeson JG, Walsh CA (2000) Neuronal migration disorders: from genetic diseases to developmental mechanisms. TINS 23:352–359PubMedGoogle Scholar
  8. Hartfuss E, Galli R, Heins N, Gotz M (2001) Characterization of CNS precursor subtypes and radial glia. Dev Biol 229:15–30PubMedCrossRefGoogle Scholar
  9. Howell BW, Gertler FB, Cooper JA (1997a) Mouse disabled (mDabl): a Src binding protein implicated in neuronal development. EMBO J 16:121–132PubMedCrossRefGoogle Scholar
  10. Howell BW, Hawkes R, Soriano P, Cooper JA (1997b) Neuronal position in the developing brain is regulated by mouse disabled-1. Nature 389:733–737PubMedCrossRefGoogle Scholar
  11. Howell BW, Herrick TM, Cooper JA (1999a) Reelin-induced tryosine phosphorylation of disabled 1 during neuronal positioning. Genes Dev 13:643–648PubMedCrossRefGoogle Scholar
  12. Howell BW, Lanier LM, Frank R, Gertler FB, Cooper JA (1999b) The disabled 1 phosphotyrosine-binding domain binds to the internalization signals of transmembrane glycoproteins and to phospholipids. Mol Cell Biol 19:5179–5188PubMedGoogle Scholar
  13. Hunter KE, Hatten ME (1995) Radial glial cell transformation to astrocytes is bidirectional: regulation by a diffusible factor in embryonic forebrain. Proc Natl Acad Sci USA 92:2061–2065PubMedCrossRefGoogle Scholar
  14. Hunter-Schaedle KE (1997) Radial glial cell development and tranformation are disturbed in reeler forebrain. J Neurobiol 33:459–472PubMedCrossRefGoogle Scholar
  15. Kwon YT, Tsai LH (2000) The role of the p35/cdk5 kinase in cortical development. Res Prob Cell Differ 30:241–253Google Scholar
  16. Kwon YT, Gupta A, Zhou Y, Nikolic M, Tsai LH (2000) Regulation of N-cadherin-mediated adhesion by the p35-Cdk5 kinase. Curr Biol 10:363–372PubMedCrossRefGoogle Scholar
  17. Lambert de Rouvroit C, Goffinet AM (1998) A new view of early cortical development. Biochem Pharmacol 56:1403–1409PubMedCrossRefGoogle Scholar
  18. Levitt P, Rakic P (1980) Immunoperoxidase localization of glial fibrillary acidic protein in radial glial cells and astrocytes of the developing rhesus monkey brain. J Comp Neurol 193:815–840PubMedCrossRefGoogle Scholar
  19. Levitt P, Cooper ML, Rakic P (1981) Coexistence of neuronal and glial precursor cells in the cerebral ventricular zone of the fetal monkey: an ultrastructural immunoperoxidase analysis. J Neurosci 1:27–39PubMedGoogle Scholar
  20. Malatesta P, Hartfuss E, Gotz M (2000) Isolation of radial glial cells by fluorescent-activated cell sorting reveals a neuronal lineage. Development 127:5253–5263PubMedGoogle Scholar
  21. Marin-Padilla M (1998) Cajal-Retzius cells and the development of the neocortex. Trends Neurosci 21:64–71PubMedCrossRefGoogle Scholar
  22. Matsumoto H, Higa HH (1966) Studies on methylazoxymethanol, the aglycone of cycasin: methy-lation of nucleic acids in vitro. Biochem J 98(2):20C-22CPubMedGoogle Scholar
  23. Meyer G, Goffinet AM, Fairen A (1999) What is a Cajal-Retzius cell? A reassessment of a classical cell type based on recent observations in the developing neocortex. Cereb Cortex 9:765–775PubMedCrossRefGoogle Scholar
  24. Miyata T, Kawaguchi A, Okano H, Ogawa M (2001) Asymmetric inheritance of radial glial fibers by cortical neurons. Neuron 31:727–741PubMedCrossRefGoogle Scholar
  25. Noctor SC, Palmer SL, Hasling T, Juliano SL (1999) Interference with the development of early generated neocortex results in disruption of radial glia and abnormal formation of neocor-tical layers. Cereb Cortex 9:121–136PubMedCrossRefGoogle Scholar
  26. Noctor SC, Flint AC, Weissman TA, Dammerman RS, Kriegstein AR (2001 a) Neurons derived from radial glial cells establish radial units in neocortex. Nature 409:714–720PubMedCrossRefGoogle Scholar
  27. Noctor SC, Palmer SL, McLaughlin DF, Juliano SL (2001b) Disruption of layers 3 and 4 during development results in altered thalamocortical projections in ferret somatosensory cortex. J Neurosci 21:3184–3195PubMedGoogle Scholar
  28. Palmer SL, Noctor SC, Jablonska B, Juliano SL (2001) Laminar specific alterations of thalamocortical projections in organotypic cultures following layer 4 disruption in ferret somatosensory cortex. Eur J Neurosci 13:1559–1571PubMedCrossRefGoogle Scholar
  29. Pinto-Lord MC, Evrard P, Caviness VS Jr (1982) Obstructed neuronal migration along radial glial fibers in the neocortex of the reeler mouse: a Golgi-EM analysis. Dev Brain Res 4:379–393CrossRefGoogle Scholar
  30. Rakic P (1971) Guidance of neurons migrating to the fetal monkey neocortex. Brain Res 33: 471–476PubMedCrossRefGoogle Scholar
  31. Rakic P (1972) Mode of cell migration to the superficial layers of fetal monkey neocortex. J Comp Neurol 145:61–83PubMedCrossRefGoogle Scholar
  32. Rice DS, Curran T (2001) Role of the reelin signaling pathway in central nervous system development. Annu Rev Neurosci 24:1005–1039PubMedCrossRefGoogle Scholar
  33. Schmechel DE, Rakic P (1979) A Golgi study of radial glial cells in developing monkey telencephalon: morphogenesis and transformation into astrocytes. Anat Embryol 156:115–152PubMedCrossRefGoogle Scholar
  34. Shatz CJ, Chun JJM, Luskin MB (1992) The role of the subplate in the development of the mammalian telencephalon. In: Peters A, Jones ED (eds) Cerebral cortex, vol 7. Plenum Press, New York, pp 35–56Google Scholar
  35. Soriano E, Alvarado-Mallart RM, Dumesnil N, Del Rio JA, Sotelo C (1997) Cajal-Retzius cells regulate the radial glia phenotype in the adult and developing cerebellum and after granule cell migration. Neuron 18:563–577PubMedCrossRefGoogle Scholar
  36. Super H, Del Rio JA, Martinez A, Perez-Sust P, Soriano E (2000) Disruption of neuronal migration and radial glia in the developing cerebral cortex following ablation of Cajal-Retzius cells. Cereb Cortex 10:602–613PubMedCrossRefGoogle Scholar
  37. Zedeck MS, Sternberg SS, Poynter RW, McGowan J (1970) Biochemical and pathological effects of methylazoxymethanol acetate, a potent carcinogen. Cancer Res 30:801–812PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2002

Authors and Affiliations

  • Marcin Gierdalski
  • Sharon L. Juliano
    • 1
  1. 1.Department of Anatomy and Cell Biology, and Program in NeuroscienceUSUHSBethesdaUSA

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