Reelin Controls Granule Cell Migration in the Dentate Gyrus by Acting on the Radial Glial Scaffold
Abstract
Reelin, synthesized and secreted by Cajal-Retzius (CR) cells in the marginal zone of the cortex, is an extracellular matrix protein important for the development of cortical layers. In reeler mutant mice lacking Reelin, there are severe malformations of neocortical and hippocampal lamination. It has been assumed that Reelin acts as a stop signal for migrating neurons. Here we show, by using the dentate gyrus as a model in in vivo studies and in vitro assays, that Reelin exerts its effects, at least in part, by acting on the radial glial scaffold required for neuronal migration. Migration defects of dentate granule cells, reminiscent of those seen in reeler mutants, are observed in tissue from patients with temporal lobe epilepsy (TLE). The extent of granule cell dispersion in TLE was found to be inversely correlated with the number of reelin mRNA synthesizing CR cells and reelin mRNA expression as revealed in quantitative RT-PCR studies. These findings show that the Reelin signaling pathway is essential for the correct positioning of human hippocampal neurons and that a Reelin deficiency is involved in the pathological changes associated with epilepsy.
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ApoER2 binds reelin during development, triggering a signaling pathway that regulates neuronal migration and the formation of laminated brain structures such as the cortex, hippocampus and cerebellum.
“ApoER2 binds the extracellular matrix protein reelin during development [4], [6], triggering a signaling pathway that regulates neuronal migration and the formation of laminated brain structures such as the cortex, hippocampus [7] and cerebellum [4]”
From Sorting nexin 17 regulates ApoER2 recycling and reelin signaling (2014) · cites this paper as [7]
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Reelin promotes hippocampal dendrite development through the VLDLR/ApoER2-Dab1 pathway
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Self-citationMolecular mechanisms in the regulation of adult neurogenesis during stress
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Reelin deficiency causes granule cell dispersion in epilepsy
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Self-citationSorting nexin 17 regulates ApoER2 recycling and reelin signaling
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Region-specific alteration of GABAergic markers in the brain of heterozygous reeler mice
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- Authors
- Frotscher, M.
- Affiliations
- University of Freiburg (DE)
- Corresponding author
- Frotscher, M.
- ORCID
- Frotscher, M.
- Venue
- Cerebral Cortex
- Publisher
- Oxford University Press (OUP)
- Published
- 2003-06-01
- Volume
- 13
- Issue
- 6
- Pages
- 634-640
- ISSN
- 1047-3211 (ISSN-L)
- 1460-2199
- OpenAlex
- W2150682032
- Cited by
- 197
- References
- 2
- Citations by year
- 2025: 5 · 2024: 2 · 2023: 3 · 2022: 7 · 2021: 9 · 2020: 5 · 2019: 5 · 2018: 7 · 2017: 5 · 2016: 7 · 2015: 6 · 2014: 11 · 2013: 12 · 2012: 13
- FWCI
- 2.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cerebral Cortex (publishedVersion)
- PubMed (publishedVersion)
- FreiDok plus (Universitätsbibliothek Freiburg) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- reelin, dentate gyrus, granule cell migration, Cajal-Retzius cells, reeler mutant mice, temporal lobe epilepsy, neuronal migration, extracellular matrix, hippocampal development
- MeSH terms
- Reelin Protein, Adult, Animals, Cell Line, Cell Movement, Epilepsy, Temporal Lobe, Gene Expression Regulation, Hippocampus, Humans, Kidney, Nerve Tissue Proteins, Neuroglia, Neurons, Reference Values, Serine Endopeptidases, Signal Transduction, Cell Adhesion Molecules, Neuronal, Extracellular Matrix Proteins, Mice, Knockout, Dentate Gyrus, Mice
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