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Journal of Neuroscience, Vol 7, 829-836, Copyright © 1987 by Society for Neuroscience
Numerical matching during cerebellar development: quantitative analysis of granule cell death in staggerer mouse chimeras
K Herrup and K Sunter
Cell death is a common yet puzzling feature of the development of many
populations of neurons in the CNS. In the invertebrate phyla, such death is
often preprogrammed; by contrast, in vertebrates, the best studied examples
of histogenetic cell death are influenced by interactions among the neurons
and their target. One attempt to explain this seemingly wasteful scheme of
development has led to the hypothesis that this target-related cell death
allows 2 populations of cells, which develop in isolation, to come into
numerical and functional balance and hence to provide an epigenetic
"buffer" mechanism to accommodate developmental variations. In the current
study we have examined the extent to which the cell death observed in the
cerebellar granule cell population serves to numerically match these
neurons with their primary postsynaptic target, the Purkinje cell.
Staggerer chimeras were made by aggregating 8-cell staggerer embryos with
embryos of wild-type genotype. The cerebella of the resulting animals
developed with widely varying numbers of normal (wild-type) Purkinje cell
targets. Although staggerer Purkinje cells were present in the chimeric
brains, these cells are intrinsically deficient in their normal
developmental program (in the mutant, because of this deficiency, 100% of
the granule cells die). Both granule cells and Purkinje cells were counted
in chimeras and several wild-type mice. The results reveal that the number
of granule cells present in these brains has a linear relationship with the
number of Purkinje cells, and that the line connecting the points
intersects the Y-axis close to the origin. These observations suggest that
numerical matching is an important function of target-related cell death in
the granule cell population.(ABSTRACT TRUNCATED AT 250 WORDS)
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