Regulation of Purkinje Cell Alignment by Reelin as Revealed with CR-50 Antibody
Open accessAbstract
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 reeler 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 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.
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Reelin proteins are assembled and anchored to the surface of a cell membrane of the Reelin-secreting cells.
“These data suggest that Reelin proteins are assembled and anchored to the surface of a cell membrane of the Reelin-secreting cells.”
From Reelin molecules assemble together to form a large protein complex, which is inhibited by the function-blocking CR-50 antibody (2000) · cites this paper as [20]
Some of the secreted Reelin is anchored to the surface of Reelin-producing cells by an unknown mechanism.
“some of the secreted Reelin is anchored to the surface of the Reelin-producing cells by an unknown mechanism.”
From Reelin molecules assemble together to form a large protein complex, which is inhibited by the function-blocking CR-50 antibody (2000) · cites this paper as [20]
CR-50 antibody has neutralizing activity of Reelin both in vitro and in vivo.
“The CR-50 antibody has neutralizing activity of Reelin both in vitro and in vivo (13, 19–21).”
From Reelin molecules assemble together to form a large protein complex, which is inhibited by the function-blocking CR-50 antibody (2000) · cites this paper as [20]
The CR-50 epitope region is essential for Reelin functions.
“This epitope region is essential for the Reelin functions, because CR-50 antibody inhibits laminar pattern formation in cortical reaggregation cultures (13), Purkinje cell alignment in cerebellar explant cultures (20), and an axonal branching pattern in the entorhinohippocampal pathway in vitro (19) and disrupts hippocampal development in vivo (21).”
From Reelin molecules assemble together to form a large protein complex, which is inhibited by the function-blocking CR-50 antibody (2000) · cites this paper as [20]
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- Authors
- Miyata, T., Nakajima, K., Mikoshiba, K., & Ogawa, M.
- Affiliations
- RIKEN (JP)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1997-05-15
- Volume
- 17
- Issue
- 10
- Pages
- 3599-3609
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6573700
- OpenAlex
- W1581713115
- Cited by
- 183
- References
- 41
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 4 · 2020: 7 · 2019: 9 · 2018: 7 · 2017: 2 · 2016: 7 · 2015: 3 · 2014: 3 · 2013: 7 · 2012: 7
- FWCI
- 4.33
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Core Research for Evolutional Science and Technology
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- reelin, cerebellar development, reeler mice, Purkinje cell migration, granule cells, cell transplantation, ventricular zone, cerebellar malformation
- MeSH terms
- Reelin Protein, Animals, Antibodies, Monoclonal, Antibody Specificity, Cell Movement, Cells, Cultured, Female, Fetus, Mice, Neurologic Mutants, Nerve Tissue Proteins, Phenotype, Pregnancy, Purkinje Cells, Serine Endopeptidases, Signal Transduction, Cell Adhesion Molecules, Neuronal, Extracellular Matrix Proteins, Gene Expression Regulation, Developmental, Mice
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