Cited by 332Neurogenesis and neuroplasticity mechanismsAxon Guidance and Neuronal SignalingDevelopmental Biology and Gene Regulation

Reelin, Rap1 and N-cadherin orient the migration of multipolar neurons in the developing neocortex

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Jossin, Yves, Cooper, Jonathan A·2011·Nature Neuroscience

Abstract

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 important downstream components of Reelin signaling in the regulation of neocortical lamination and postnatal hippocampal dendritogenesis.

    “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).”
  • Independent of PI3K, Reelin stabilizes actin by triggering C3G activation of Rap1 through Crk family proteins.

    “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).”
  • C3G activation of Rap1 through Crk family proteins is essential for normal neocortical lamination and postnatal hippocampal dendritogenesis.

    “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).”

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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
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
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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