Abnormal dispersion of a Purkinje cell subset in the mouse mutant cerebellar deficient folia (cdf)

Purkinje cells of different molecular phenotypes subdivide the cortex of th e cerebellum both rostrocaudally into parasagittal bands and mediolaterally into transverse zones. Superimposed on the Purkinje cell compartmentation, the cerebellar cortex is pleated into a reproducible array of lobes and lo bules. During cerebellar development, Purkinje cell bands are formed throug h the rostrocaudal dispersal. of embryonic clusters, triggered primarily by a Reelin-dependent signaling pathway. In the naturally occurring mouse mut ant cerebellar deficient folia (cdf), there is a failure of Purkinje cell d ispersion that results in widespread Purkinje cell ectopia in the adult. Th e ectopia is restricted primarily to that subset of Purkinje cells that doe s not express zebrin II/aldolase C and that forms ectopic clusters in among the cerebellar nuclei. Most Purkinje cells that express zebrin II are loca ted normally in a monolayer. Thus, the cerebellum of cdf mutants has a fail ure of Purkinje cell dispersion that is confined primarily to a zebrin II-n egative (zebrin II-) subpopulation. Despite the Purkinje cell ectopia, the parasagittal band organization of the cerebellum is still clear. The shorte ning of the cortex is distributed evenly over all lobules, with the result that transverse expression boundaries are relocated with respect to the lob ules and fissures. The number of Purkinje cells in the cdf/cdf cerebellum i s similar to the number in littermate controls. Therefore, it appears that the lesion in cdf results in the failure of a zebrin II- Purkinje cell subs et to disperse either due to a cell intrinsic defect or due to an abnormal interaction between the Purkinje cells and either granule cells or afferent inputs. J. Comp. Neurol. 436. 42-51, 2001. (C) 2001 Wiley-Liss, Inc.