CEREBELLAR HISTOGENESIS AS SEEN IN IDENTIFIED CELLS OF NORMAL-REELER MOUSE CHIMERAS

The potential contribution of cell-cell interactions and extracellular factors to cytoarchitectonic abnormalities in the cerebellum of the r eeler mutant mouse was investigated by forming chimeras between the re eler and normal animals. The strain origin of Purkinje cells, granule cells and Golgi epithelial cells was immunohistologically identified w ith a strain-specific antibody. We analyzed 16 overt coat color chimer as, 10 reeler <-> C3H and 6 reeler <-> Balb/c. Abnormal behavioral tra its of reeler were rescued in all chimeras. However, cerebellar histol ogy was more affected in reeler tt C3H chimeras than in reeler <-> Bal b/c, Purkinje cells from the normal genotype occupy ectopic positions, and reeler genotype cells are arranged appropriately in the same chim eric cerebellum. We also obtained histologically normal chimeras with a significantly high contribution of the reeler genotype in Purkinje c ells, Golgi epithelial cells and granule cells. These results clearly indicate that the abnormal cell positioning and cytoarchitecture of ne urons and glia in the reeler is caused by a deficiency of extracellula r environments, but is not determined cell-autonomously. The present d ata on chimeric mice suggest that Reelin is one of the important extra cellular environmental factors that affects indirectly radial glial ce lls during cerebellar histogenesis.