Purkinje cell dendrites in staggerer<-->wild type mouse chimeras lack the aberrant morphologies found in lurcher<-->wild type chimeras.
In lurcher<-->wild type mouse chimeras (lurcher chimeras), mutant Purkinje cells are transiently present and probably provide target support for afferent granule cells during the sensitive period of target-dependent cell death. Previous studies demonstrate that wild type Purkinje cells in the cerebella of mature lurcher chimeras often have atrophic dendritic morphologies, leading to the hypothesis that developmental deafferentation of wild type Purkinje cells occurs uniquely in lurcher chimeras following the period of mutant Purkinje cell loss. Other studies document the survival of a disproportionately large number of granule cells in these animals. Based on cell birthdate analyses, the hypothesis further proposes that deafferentation induces an up-regulation of trophic activity among the Purkinje cell population and the consequent rescue of late generated granule cells that might otherwise be lost to target related cell death. In the present study, we take advantage of phenotypic differences between the staggerer and lurcher mutations to test this hypothesis. While staggerer<-->wild type chimeras (staggerer chimeras) resemble lurcher chimeras in several respects, including extensive cell loss, they differ in that staggerer Purkinje cells never provide target support for granule cells. Hence the hypothesis predicts that Purkinje cells in these animals should not exhibit the atrophic morphologies found in lurcher chimeras. We have developed a new semiquantitative method for scoring dendritic morphology in a large number of Golgi-impregnated cells. We have used this method to characterize the distribution of wild type Purkinje cell morphologies in staggerer chimeras, and to compare these with the corresponding distributions of morphologies in lurcher chimeras and wild type<-->wild type chimeras. We find that morphologies in staggerer chimeras closely resemble those in control chimeras. Furthermore, Purkinje cells in both staggerer and wild type chimeras differ significantly from those in lurcher chimeras. These results confirm a direct prediction of the hypothesis.
Soha
J M
JM
E.K. Shriver Center, Waltham, Massachusetts 02254.
Herrup
K
K
D000818:Animals; D002678:Chimera / Q000502:physiology*; D003712:Dendrites / Q000648:ultrastructure*; D051379:Mice; D008818:Mice, Neurologic Mutants / Q000033:anatomy & histology*; D011689:Purkinje Cells / Q000648:ultrastructure*