Springer Nature is making Coronavirus research free. View research | View latest news | Sign up for updates

Developmental analysis of GFAP immunoreactivity in the cerebellum of the meander tail mutant mouse

  • 70 Accesses

  • 1 Citations


It is thought that Bergmann glial fibers assist in the inward migration of granule cells. Model systems in which there is a perturbation of either the migrating cells or the glial cell population have been useful in understanding the migratory process. In the meander tail mutant mouse, the anterior cerebellar region is agranular, whereas the posterior cerebellum is relatively unaffected by the mutation. This study presents a qualitative analysis of the development of cerebellar radial glia in mea/mea and +/mea mice aged from postnatal day 0 to adult, using an antibody against the glia specific antigen, glial fibrillary acidic protein. The results indicate a slight delay in the onset of immunoreactivity in the mea/mea cerebellum and abnormal glial formation in the anterior and posterior regions by postnatal day 5. At postnatal day 11, the full complement of labeled fibers appears to be present and although they appear abnormal in formation, they eventually reach the surface and terminate in oddly shaped and irregularly spaced endfeet. In adult mea/mea and +/mea mice, as compared to the early postnatal stages, there is a significant reduction in GFAP immunoreactive fibers. Cresyl violet stained adult mea/mea sections revealed the presence of ectopic granule cells in radial columns and small clumps at the surface of and within the molecular layer of the caudal cerebellum. Quantitative analyses revealed a 4- to 5-fold increase in the number of ectopic granule cells in lobule VIII of the mea/mea when compared with the +/mea cerebellum. These results suggest that the radial glia in the mea/mea cerebellum exhibit some uncharacteristic morphologies, but that these abnormalities are most likely the consequence of environmental alterations produced by the mutant gene.

This is a preview of subscription content, log in to check access.


  1. Altman J, Bayer SA (1978) Prenatal development of the cerebellar system in the rat I. Cytogenesis and histogenesis of the deep nuclei and the cortex of the cerebellum. J Comp Neurol 179: 23–48

  2. Alvarez Otero R, Sotelo C, Alvarado-Mallart R-M (1993) Chick/quail chimeras with partial cerebellar grafts: an analysis of the origin and migration of cerebellar cells. J Comp Neurol 333: 597–615

  3. Antonicek H, Persogn E, Schachner M (1987) Biochemical and functional characterization of a novel neuron-glia adhesion molecule that is involved in neuronal migration. J Cell Biol 104: 1587–1595

  4. Berciano MT, Lafarga M (1988) Colony-forming ectopic granule cells in the cerebellar primary fissure of normal adult rats: a morphologic and morphometric study. Brain Res 439: 169–178

  5. Berciano MT, Conde B, Lafarga M (1990) Interactions between astroglia and ectopic granule cells in the cerebellar cortex of normal adult rats: a morphological and cytochemical study. Exp Brain Res 80: 397–408

  6. Bignami A, Dahl D (1973) Differentiation of astrocytes in the cerebellar cortex and the pyramidal tracts of the newborn rat. An immunofluorescence study with antibodies to a protein specific to astrocytes. Brain Res 49: 393–402

  7. Bovolenta P, Liem RKH, Mason CA (1984) Development of cerebellar astroglia: transitions in form and cytoskeletal content. Dev Biol 102: 248–259

  8. Choi BH, Lapham LW (1980) Evolution of Bergmann glia in developing human fetal cerebellum: a Golgi, electron-microscopic and imunofluorescent study. Brain Res 190: 369–383

  9. Fisher M, Trimmer P, Ruthel G (1993) Bergmann glia require continuous association with Purkinje cells for normal phenotype expression. Glia 8: 172–182

  10. Goldowitz D (1989) The weaver granuloprival phenotype is due to intrinsic action of the mutant locus in granule cells: evidence from homozygous weaver chimeras. Neuron 2: 1565–1575

  11. Goldowitz D, Mullen RJ (1982) Granule cell as a site of gene action in the weaver mouse cerebellum: evidence from heterozygous mutant chimeras. J Neurosci 2: 1474–1485

  12. Hamre KM, Goldowitz D (1994) The meander tail gene has multiple effects on cerebellar granule cell development and survival. Soc Neurosci Abstr 20: 1489

  13. Hatten ME (1985) Neuronal regulation of astroglial morphology and proliferation in-vitro. J Cell Biol 100: 384–396

  14. Hatten ME, Furie MB, Rifkin DB (1982) Binding of developing mouse cerebellar cells to fibronectin: a possible mechanism for the formation of the external granular layer. J Neurosci 2: 1195–1206

  15. Hatten ME, Liem RKH, Mason CA (1984) Defects in specific associations between astroglia and neurons occur in microcultures of weaver mouse cerebellar cells. J Neurosci 4: 1163–1172

  16. Heckroth JA, Atkintunde A, Grishkat H, Eisenman LM (1994) Cytology of the cerebellar cortex in the meander tail mutant mouse. Soc Neurosci Abstr 20: 1743

  17. Hollander WF, Waggie KS (1977) Meander tail: A recessive mutant located in chromosome 4 of the mouse. J Hered 68: 403–406

  18. Hynes RO, Patel R, Miller RH (1986) Migration of neuroblasts along preexisting axonal tracts during prenatal cerebellar development. J Neurosci 6: 867–876

  19. Mugnaini E (1972) The histology and cytology of the cerebellar cortex. In: Larsell O, Jansen J (eds) The comparative anatomy and histology of the cerebellum: the human cerebellum, cerebellar connections, and cerebellar cortex. University of Minnesota Press, Minneapolis, pp 201–251

  20. Napieralski JA, Eisenman LM (1993) Developmental analysis of the external granular layer in the meander tail mutant mouse: do cerebellar microneurons have independent progenitors? Dev Dyn 97: 244–254

  21. Napieralski JA, Eisenman LM (1995) Further evidence for a unique developmental compartment in the cerebellum of the meander tail mutant mouse as revealed by the quantitative analysis of Purkinje cells. J Comp Neurol 364: 718–728

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

  23. Rakic P, Sidman RL (1973) Weaver mutant mouse cerebellum: defective neuronal migration secondary to abnormality of Bergmann glia. Proc Natl Acad Sci USA 70: 240–244

  24. Ross ME, Fletcher C, Mason CA, Hatten ME, Heintz N (1990) Meander tail reveals a discrete developmental unit in the mouse cerebellum. Proc Natl Acad Sci USA 87: 4189–4192

  25. Shiga T, Ichikawa M, Hirata Y (1983) A Golgi study of Bergmann glial cells in developing rat cerebellum. Anat Embryol 167: 191–201

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

  27. Smeyne RJ, Goldowitz D (1989) Development and death of external granular layer cells in the weaver mouse cerebellum: a quantitative study. J Neurosci 9: 1608–1620

  28. Sotelo C, Changeux JP (1974) Bergmann fibers and granular cell migration in the cerebellum of homozygous weaver mutant mouse. Brain Res 77: 484–491

  29. Trenkner E, Smith D, Segil N (1984) Is cerebellar granule cell migration regulated by an internal clock? J Neurosci 4: 2850–2855

  30. Wang L-C, Baird DH, Hatten ME, Mason CA (1994) Astroglial differentiation is required for support of neurite outgrowth. J Neurosci 14: 1395–3207

  31. Yuasa S, Kitoh J, Oda S, Kawamura K (1993) Obstructed migration of Purkinje cells in the developing cerebellum of the reeler mutant mouse. Anat Embryol 188: 317–329

Download references

Author information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Grishkat, H.L., Schwartz, E., Jain, G. et al. Developmental analysis of GFAP immunoreactivity in the cerebellum of the meander tail mutant mouse. Anat Embryol 194, 135–146 (1996).

Download citation

Key words

  • Glial fibrillary acidic protein
  • Bergmann glial fibers
  • Granule cells
  • Cerebellar mutation
  • Purkinje cell