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Reelin, Rap1 and N-cadherin orient the migration of multipolar neurons in the developing neocortex
Open accessAbstract
Projection neurons migrate from the ventricular zone to the neocortical plate during the development of the mouse brain. Their overall movement is radial, but they become multipolar and move nonradially in the intermediate zone. Here we show that Reelin, the Rap1 GTPase and N-cadherin (NCad) are important for multipolar neurons to polarize their migration toward the cortical plate. Inhibition and rescue experiments indicated that Reelin regulates migration through Rap1 and Akt, and that the Rap1-regulated GTPases RalA, RalB, Rac1 and Cdc42 are also involved. We found that Rap1 regulated the plasma membrane localization of NCad and NCad rescued radial polarization when Rap1 was inhibited. However, inhibition of Rap1 or NCad had little effect on glia-dependent locomotion. We propose a multistep mechanism in which Reelin activates Rap1, Rap1 upregulates NCad, and NCad is needed to orient cell migration.
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“Crk family proteins are also important downstream components of the Reelin signaling pathway in the regulation of both neocortical lamination and postnatal hippocampal dendritogenesis (12, 13) (Fig. 1E).”
From Reelin: Neurodevelopmental Architect and Homeostatic Regulator of Excitatory Synapses (2017) · cites this paper as [13]
In the citing paper
“independent of PI3K, Reelin stabilizes actin by triggering C3G activation of Rap1 through Crk family proteins (Crk), which is essential for normal neocortical lamination and postnatal hippocampal dendritogenesis (12, 13).”
From Reelin: Neurodevelopmental Architect and Homeostatic Regulator of Excitatory Synapses (2017) · cites this paper as [13]
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“independent of PI3K, Reelin stabilizes actin by triggering C3G activation of Rap1 through Crk family proteins (Crk), which is essential for normal neocortical lamination and postnatal hippocampal dendritogenesis (12, 13).”
From Reelin: Neurodevelopmental Architect and Homeostatic Regulator of Excitatory Synapses (2017) · cites this paper as [13]
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Metadata
- Authors
- Jossin, Y., & Cooper, J. A.
- Affiliations
- Fred Hutch Cancer Center (US)
- Corresponding author
- Jossin, Yves
- Cooper, Jonathan A
- Venue
- Nature Neuroscience
- Published
- 2011-04-24
- Volume
- 14
- Issue
- 6
- Pages
- 697-703
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC3102785
- OpenAlex
- W2118947728
- Cited by
- 332
- References
- 50
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 19 · 2023: 15 · 2022: 17 · 2021: 14 · 2020: 24 · 2019: 26 · 2018: 34 · 2017: 26 · 2016: 27 · 2015: 35 · 2014: 31 · 2013: 24 · 2012: 20
- FWCI
- 8.40
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Libraries (Université catholique de Louvain (UCL), l'Université de Namur (UNamur) and the Université Saint-Louis (USL-B)) (submittedVersion, other-oa)
- Funders
- National Cancer Institute (R37CA041072, CA41072, R01CA041072)
- 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, Rap1 GTPase, N-cadherin, neuronal migration, multipolar neurons, cortical plate, neocortex development, projection neurons, Akt signaling, RalA, RalB, Rac1, Cdc42, cell polarity, intermediate zone
- MeSH terms
- Reelin Protein, Animals, Cell Differentiation, Cell Movement, Mice, Inbred Strains, Nerve Tissue Proteins, Neurons, Serine Endopeptidases, Cell Adhesion Molecules, Neuronal, Cadherins, Extracellular Matrix Proteins, Neocortex, rap1 GTP-Binding Proteins, Mice
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