How does Reelin control neuronal migration and layer formation in the developing mammalian neocortex?
Abstract
The mammalian neocortex has a laminar structure that develops in a birth-date-dependent "inside-out" pattern. Its layered structure is established by neuronal migration accompanied by sequential changes in migratory mode regulated by several signaling cascades. Although Reelin was discovered about two decades ago and is one of the best known molecules that is indispensable to the establishment of the "inside-out" neuron layers, the cellular and molecular functions of Reelin in layer formation are still largely unknown. In this review article, we summarize our recent understanding of Reelin's functions during neuronal migration. Reelin acts in at least two different steps of neuronal migration: the final step of neuronal migration (somal/terminal translocation) just beneath the marginal zone (MZ) and the regulation of cell polarity step when the neurons change their migratory mode from multipolar migration to locomotion. During the translocation mode, Reelin activates integrin α5β1 through an intracellular pathway that triggers the translocation and activates N-cadherin in concert with the nectin-afadin system. Reelin is also involved in the termination of neuronal migration by degrading Dab1 via the SOCS7-Cullin5-Rbx2 system, and Reelin has been found to induce the birth-date-dependent neuronal aggregation in vivo. Based on these findings, we hypothesize that the molecular function of Reelin during neuronal migration is to control cell-adhesiveness during development by regul…
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VLDLR and ApoER2 are key signaling receptors in the Reelin pathway and critical for proper cortical and cerebellar development as well as neuronal plasticity.
“These proteins are key signaling receptors in the Reelin pathway (Poirier et al., 2008; Roubtsova et al., 2011; Sekine et al., 2014) and hence critical for proper cortical and cerebellar development as well as neuronal plasticity (Trommsdorff et al., 1999; Armstrong et al., 2019).”
From PCSK9 deficiency alters brain lipid composition without affecting brain development and function (2023) · cites this paper as Sekine et al., 2014
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Trekking across the Brain: The Journey of Neuronal Migration
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Reelin, Rap1 and N-cadherin orient the migration of multipolar neurons in the developing neocortex
Jossin, Y., & Cooper, J. A. (2011) · Nature Neuroscience · doi:10.1038/nn.2816 · Cited by 332 · see citing works
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Reelin and neuropsychiatric disorders
Ishii, K., Kubo, K.-I., & Nakajima, K. (2016) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2016.00229 · Cited by 185 · see citing works
Self-citationPCSK9 deficiency alters brain lipid composition without affecting brain development and function
Pärn, A., Olsen, D., Tuvikene, J., Kaas, M., Borisova, E., Bilgin, M., Elhauge, M., Vilstrup, J., Madsen, P., Ambrozkiewicz, M. C., et al. (2023) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.1084633 · Cited by 16 · see citing works
- Authors
- Sekine, K., Kubo, K.-I., & Nakajima, K.
- Affiliations
- Keio University (JP)
- Corresponding author
- Nakajima, Kazunori
- Venue
- Neuroscience Research
- Publisher
- Elsevier BV
- Published
- 2014-09
- Volume
- 86
- Pages
- 50-58
- ISSN
- 0168-0102 (ISSN-L)
- OpenAlex
- W2016327001
- Cited by
- 124
- References
- 5
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 4 · 2023: 6 · 2022: 4 · 2021: 10 · 2020: 18 · 2019: 14 · 2018: 12 · 2017: 16 · 2016: 14 · 2015: 14 · 2014: 3
- FWCI
- 1.63
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Strategic Research Program for Brain Sciences (10036057)
- Ministry of Education, Culture, Sports, Science, and Technology (22111004, 25640039, 25116522, 26430075)
- 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, neuronal migration, alpha5beta1 integrin, N-cadherin, cell polarity, adhesion molecules, birth date, marginal zone
- MeSH terms
- Reelin Protein, Animals, Cell Movement, Humans, Mammals, Nerve Tissue Proteins, Neurons, Serine Endopeptidases, Signal Transduction, Cell Adhesion Molecules, Neuronal, Extracellular Matrix Proteins, Neocortex, Neurogenesis
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