Reelin signaling directly affects radial glia morphology and biochemical maturation
Open accessAbstract
Radial glial cells are characterized, besides their astroglial properties,by long radial processes extending from the ventricular zone to the pial surface, a crucial feature for the radial migration of neurons. The molecular signals that regulate this characteristic morphology, however, are largely unknown. We show an important role of the secreted molecule reelin for the establishment of radial glia processes. We describe a significant reduction in ventricular zone cells with long radial processes in the absence of reelin in the cortex of reeler mutant mice. These defects were correlated to a decrease in the content of brain lipid-binding protein (Blbp) and were detected exclusively in the cerebral cortex, but not in the basal ganglia of reeler mice. Conversely, reelin addition in vitro increased the Blbp content and process extension of radial glia from the cortex, but not the basal ganglia. Isolation of radial glia by fluorescent-activated cell sorting showed that these effects are due to direct signaling of reelin to radial glial cells. We could further demonstrate that this signaling requires Dab1, as the increase in Blbp upon reelin addition failed to occur in Dab1-/-mice. Taken together, these results unravel a novel role of reelin signaling to radial glial cells that is crucial for the regulation of their Blbp content and characteristic morphology in a region-specific manner.
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The formation of vertical processes emanating from radial glia cells requires proper Reelin signaling.
“Because the formation of vertical processes emanating from these cells requires proper Reelin signaling (39) and the LXR null mice have substantially reduced Idol expression (13), it remains to be seen whether Idol contributes to the observed migratory defect.”
From The E3 ubiquitin ligase IDOL induces the degradation of the low density lipoprotein receptor family members VLDLR and ApoER2 (2010) · cites this paper as [39]
The Discussion says Reelin is a necessary factor for radial process elongation or maintenance in the reeler mutant cortex. But it also says some radial glia extend long processes without Reelin and that radial glia in other CNS regions do not require its signaling. The claim omits this regional and cellular qualification. (LLM, conf=0.88)
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Cites
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Self-citationReelin Is a Ligand for Lipoprotein Receptors
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Regulation of Radial Glial Survival by Signals from the Meninges
Radakovits, R., Barros, C. S., Belvindrah, R., Patton, B., & Muller, U. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.5537-08.2009 · Cited by 135 · see citing works
Emerging topics in Reelin function
Förster, E., Bock, H. H., Herz, J., Chai, X., Frotscher, M., & Zhao, S. (2010) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2010.07222.x · Cited by 130 · see citing works
Self-citationReelin in the years: controlling neuronal migration and maturation in the mammalian brain
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Canonical and non-canonical Reelin signaling
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Self-citationAlcántara, S., Pozas, E., Ibañez, C. F., & Soriano, E. (2006) · Cerebral Cortex · doi:10.1093/cercor/bhi128 · Cited by 71 · see citing works
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Self-citation
- Authors
- Hartfuss, E., Förster, E., Bock, H. H., Hack, M. A., Leprince, P., Luque, J. M., Herz, J., Frotscher, M., & Götz, M.
- Affiliations
- Max Planck Institute of Neurobiology (DE)
- University of Freiburg (DE)
- Max Planck Society (DE)
- Consejo Superior de Investigaciones Científicas (ES)
- Max-Planck-Institute of Neurobiology, Neuronal Specification, Am Klopferspitz 18a, D-82152 Martinsried, Germany
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2003-10-01
- Volume
- 130
- Issue
- 19
- Pages
- 4597-4609
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- OpenAlex
- W1981941572
- Cited by
- 237
- References
- 5
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 3 · 2023: 5 · 2022: 7 · 2021: 3 · 2020: 16 · 2019: 5 · 2018: 3 · 2017: 7 · 2016: 7 · 2015: 12 · 2014: 8 · 2013: 13 · 2012: 11
- FWCI
- 3.53
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Locations
- Development (publishedVersion)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Max Planck Digital Library (submittedVersion)
- FreiDok plus (Universitätsbibliothek Freiburg) (submittedVersion)
- Open Repository and Bibliography (University of Liège) (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Alexander von Humboldt-Stiftung
- Deutsche Forschungsgemeinschaft (SFB 505)
- Fonds De La Recherche Scientifique - FNRS
- Generalitat Valenciana
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R37HL063762)
- 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 signaling, radial glia, brain lipid-binding protein, Dab1, reeler mutant mice, cerebral cortex, basal ganglia, radial migration, ventricular zone, cell morphology
- MeSH terms
- Fatty Acid-Binding Protein 7, Reelin Protein, Animals, Carrier Proteins, Cell Differentiation, Cerebral Cortex, Mice, Inbred C57BL, Mice, Neurologic Mutants, Nerve Tissue Proteins, Neuroglia, Neurons, Recombinant Fusion Proteins, Serine Endopeptidases, Signal Transduction, Cell Adhesion Molecules, Neuronal, Extracellular Matrix Proteins, Cell Surface Extensions, Cell Size, Fatty Acid-Binding Proteins, Mice
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