Abstract
Previous work showed that in cerebella of mice homozygous for the autosomal mutation weaver, wv, most postmitotic granule cell neurons die during the first 2 weeks after birth close to their site of genesis in the external granular layer. Analysis of the less severely affected heterozygotes by electron microscopy and autoradiography indicates that granule cell death occurs several days after cell genesis and is secondary to failure of their somas to migrate across the molecular layer to the granular layer. This migration defect in turn appears secondary to a hitherto unrecognized disorder of Bergmann glial cells, the cells that normally guide the young neurons in their migration. In +/wv cerebella, Bergmann glial processes are enlarged and irregular in caliber, electronlucent, and often vacuolated; in wv/wv, Bergmann cell processes are almost absent. The primary genetic abnormality remains undefined, but the gene dosage effect, here recognized at a cellular level for the first time in a mammalian neurological mutant, suggests that even though neuronal death serves as the most prominent and clinically relevant phenotypic expression, the Bergmann glial abnormality may actually be closer to the primary cellular target of the wv genetic locus.
Keywords: cerebellar development, neuron-glial cell interaction, neurological mutant mice
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