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Journal of Neuroscience, Vol 9, 1608-1620, Copyright © 1989 by Society for Neuroscience
Development and death of external granular layer cells in the weaver mouse cerebellum: a quantitative study
RJ Smeyne and D Goldowitz
Department of Anatomy, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Previous studies have identified the cerebellar granule cell as a primary
site of gene action in the weaver mutant mouse. The temporal expression of
the weaver mutant granule cell phenotype has not been fully investigated.
To identify early postnatal expression of the weaver mutant phenotype, we
quantitated 4 parameters of cerebellar development in postnatal day 0, 2,
4, 6, and 8 +/+, wv/+, and wv/wv mice: (1) cerebellar area, (2) cells in
the external granule layer (EGL), (3) number of mitotic figures in the EGL,
and (4) number of pyknotic figures in the EGL. Qualitative observations
suggest a generalized retardation in the development of wv/wv and wv/+ EGL
cells compared with the +/+ cells. Quantitatively, the earliest detectable
mutant phenotype in wv/wv and wv/+ cerebella is the increased presence of
cell death in the EGL, apparent at the day of birth. Degenerating cells in
the EGL, the majority of which are found in the postmitotic zone of this
layer, contain abnormally clumped heterochromatin, suggestive of "nuclear"
cell death. Previous hypotheses concerning the mechanism of weaver gene
action have suggested that granule cells die due to their inability to
migrate from the EGL. The time course, mode, and spatial organization of
cell death found in the present studies lead us to suggest that an earlier
event in granule cell development, such as the exit of neuroblasts from the
cell cycle or axonogenesis, is affected by the weaver gene.
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