Journal of Neuroscience, Vol 9, 3454-3462, Copyright © 1989 by Society for Neuroscience
Numerical matching between granule and Purkinje cells in lurcher chimeric mice: a hypothesis for the trophic rescue of granule cells from target-related cell death
MW Vogel, K Sunter and K Herrup
Department of Human Genetics, Yale Medical School, New Haven, Connecticut 06510.
Previous studies of wild-type mice or mutant-wild-type mouse chimeras using
the neurological mutant staggerer have supported a numerical matching
hypothesis for target-related cell death. However, analyses of chimeras of
a second neurological mutant, lurcher, have suggested that there may be
significant flexibility in the relationship between the numbers of pre- and
postsynaptic neurons. Whereas in staggerer chimeras there is a strict
proportionality between the number of cerebellar granule cells and their
postsynaptic target, the Purkinje cells, in lurcher chimeras, Wetts and
Herrup (1983) report a relative increase in granule cell survival. We have
reexamined the numerical matching between Purkinje and granule cells in an
additional 5 lurcher----wild- type and 4 wild-type----wild-type chimerase.
Our findings confirm and extend the results of the previous study to show
that there is a close correlation between the number of granule and
Purkinje cells in +/Lc chimeras, but for any given number of Purkinje cells
in the +/Lc chimeras, more granule cells survive than in staggerer chimeras
or inbred mouse strains. Whereas the ratio of granule to Purkinje cells in
staggerer chimeras or inbred mouse strains is constant across all target
sizes, in +/Lc chimeras the ratio of granule cells to Purkinje cells
increases as the number of target neurons decreases. It seems likely that
the increased granule cell survival is somehow related to the delayed
degeneration of the +/Lc fraction of target cells in the +/Lc chimeras.
Among the possible explanations for the observed results, we favor the
hypothesis that a trophic factor is produced in +/Lc chimeras in response
to the deafferentation of Purkinje cells that is capable of rescuing
granule cells from target-related cell death. Our preference is based, in
part, on observations of the state of the dendritic tree of the wild-type
Purkinje cells that survive in +/Lc chimeras (Caddy et al., 1986).
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