Regulation of Purkinje cell alignment by Reelin as revealed with CR-50 antibody

Takaki Miyata, Kazunori Nakajima, Katsuhiko Mikoshiba, Masaharu Ogawa

Research output: Contribution to journalArticle

143 Citations (Scopus)

Abstract

Cerebellar Purkinje cells are generated in the ventricular zone, migrate outward, and finally form a monolayer in the cortex. In reeler mice, however, most Purkinje cells cluster abnormally in subcortical areas. Reelin, the candidate feeler gene 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 an in vitro system and a transplantation approach to analyze the function of Reelin. Explant culture for 7 d of cerebella isolated from wild-type and reeler mice 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 a reeler-like, clustered pattern. On the other hand, when reeler explants lacking Reelin were crowned with an artificial layer of Reelin+ granule cells, some Reelin molecules were distributed into a superficial zone of the reeler explants, 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 in feeler cerebella. 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.

Original languageEnglish
Pages (from-to)3599-3609
Number of pages11
JournalJournal of Neuroscience
Volume17
Issue number10
DOIs
Publication statusPublished - 1997

Keywords

  • CR- 50
  • Purkinje cell
  • cell migration
  • cerebellum
  • explant culture
  • granule cell
  • layer formation
  • reeler mutant mouse
  • reelin
  • transplantation

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Regulation of Purkinje cell alignment by Reelin as revealed with CR-50 antibody'. Together they form a unique fingerprint.

  • Cite this