RT Journal Article
SR Electronic
T1 Regulation of Purkinje Cell Alignment by Reelin as Revealed with CR-50 Antibody
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 3599
OP 3609
DO 10.1523/JNEUROSCI.17-10-03599.1997
VO 17
IS 10
A1 Takaki Miyata
A1 Kazunori Nakajima
A1 Katsuhiko Mikoshiba
A1 Masaharu Ogawa
YR 1997
UL http://www.jneurosci.org/content/17/10/3599.abstract
AB Cerebellar Purkinje cells are generated in the ventricular zone, migrate outward, and finally form a monolayer in the cortex. Inreeler mice, however, most Purkinje cells cluster abnormally in subcortical areas. Reelin, the candidatereeler 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 andreeler 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 areeler-like, clustered pattern. On the other hand, whenreeler explants lacking Reelin were crowned with an artificial layer of Reelin+ granule cells, some Reelin molecules were distributed into a superficial zone of thereeler 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 reeler 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.