Regulation of Purkinje Cell Alignment by Reelin as Revealed with CR-50 Antibody

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Abstract
Cerebellar Purkinje cells are generated in the ventricular zone, migrate outward, and finally form a monolayer in the cortex. Inreelermice, however, most Purkinje cells cluster abnormally in subcortical areas. Reelin, the candidatereelergene product recognized by the CR-50 monoclonal antibody, is concentrated in a cortical zone along which Purkinje cells are aligned linearly, implying that it may regulate their alignment. We used anin vitrosystem and a transplantation approach to analyze the function of Reelin.Explant culture for 7 d of cerebella isolated from wild-type andreelermice at embryonic day 13 (E13) reproduced in a phenotype-dependent manner the two distinct arrangement patterns (linear vs clustered) of Purkinje cells. Extensive CR-50 binding to wild-type explants converted the linear pattern into areeler-like, clustered pattern. On the other hand, whenreelerexplants lacking Reelin were crowned with an artificial layer of Reelin+granule cells, some Reelin molecules were distributed into a superficial zone of thereelerexplants, and Purkinje cells formed a linear pattern along the Reelin-rich overlay. This “rescue” effect was also inhibited by CR-50. Hence, Reelin is involved in the Purkinje cell alignment, and the lack of this activity may explain the malformation inreelercerebella.We further injected Reelin+granule cells into the fourth ventricle of E12–13 mice. Extensive incorporation of the injected Reelin+cells into the ventricular zone, but not of Reelin−cells, forced Purkinje cells of the host cerebella to form an aberrant layer, suggesting that premigratory Purkinje cells may already be responsive to Reelin or Reelin-related signals.