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Plexin-B2, But Not Plexin-B1, Critically Modulates Neuronal Migration and Patterning of the Developing Nervous System In Vivo
Open accessAbstract
Semaphorins and their receptors, plexins, have emerged as important cellular cues regulating key developmental processes. B-type plexins directly regulate the actin cytoskeleton in a variety of cell types. Recently, B-type plexins have been shown to be expressed in striking patterns in the nervous system over critical developmental windows. However, in contrast to the well characterized plexin-A family, the functional role of plexin-B proteins in neural development and organogenesis in vertebrates in vivo is not known. Here, we have elucidated the functional contribution of the two neuronally expressed plexin-B proteins, Plexin-B1 or Plexin-B2, toward the development of the peripheral nervous system and the CNS by generating and analyzing constitutive knock-out mice. The development of the nervous system was found to be normal in mice lacking Plexin-B1, whereas mice lacking Plexin-B2 demonstrated defects in closure of the neural tube and a conspicuous disorganization of the embryonic brain. After analyzing mutant mice, which bypassed neural tube defects, we observed a key requirement for Plexin-B2 in proliferation and migration of granule cell precursors in the developing dentate gyrus, olfactory bulb, and cerebellum. Furthermore, we identified semaphorin 4C as a high-affinity ligand for Plexin-B2 in binding and functional assays. Semaphorin 4C stimulated activation of ErbB-2 and RhoA via Plexin-B2 and enhanced proliferation and migration of granule cell precursors. Semaphorin 4C-induced proliferation of ventricular zone neuroblasts was abrogated in mice lacking Plexin-B2. These genetic and functional analyses reveal a key requirement for Plexin-B2, but not Plexin-B1, in patterning of the vertebrate nervous system in vivo.
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“Plexin-B1 knockout (KO) mice are viable and fertile, with no overt neurodevelopmental defects21, 22.”
From Regulation of cell distancing in peri-plaque glial nets by Plexin-B1 affects glial activation and amyloid compaction in Alzheimer’s disease (2024) · cites this paper as [21]
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Metadata
- Authors
- Deng, S., Hirschberg, A., Worzfeld, T., Penachioni, J. Y., Korostylev, A., Swiercz, J. M., Vodrazka, P., Mauti, O., Stoeckli, E. T., Tamagnone, L., Offermanns, S., & Kuner, R.
- Affiliations
- Heidelberg University (DE)
- University of Turin (IT)
- University of Zurich (CH)
- Venue
- Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2007-06-06
- Volume
- 27
- Issue
- 23
- Pages
- 6333-6347
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6672150
- OpenAlex
- W1977584759
- Cited by
- 121
- References
- 52
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 10 · 2023: 9 · 2022: 11 · 2021: 8 · 2020: 10 · 2019: 6 · 2018: 8 · 2017: 7 · 2016: 4 · 2015: 5 · 2014: 5 · 2013: 1 · 2012: 8
- FWCI
- 2.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- Deutsche Forschungsgemeinschaft (SFB 488)
- Universität Heidelberg
- Ministero dell’Istruzione, dell’Università e della Ricerca (PRIN2005)
- Associazione Italiana per la Ricerca sul Cancro
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- Plexin-B2, Plexin-B1, semaphorin receptors, neural tube closure, neural tube defects, neuronal migration, granule cell precursors, dentate gyrus, olfactory bulb, cerebellum, ERBB2, RhoA, actin cytoskeleton, peripheral nervous system development, knockout mice
- MeSH terms
- Animals, Cell Movement, Chlorocebus aethiops, Cerebellum, Humans, Nerve Tissue Proteins, Nervous System, Receptors, Cell Surface, Prosencephalon, Mice, Knockout, Body Patterning, COS Cells, Organogenesis, Cell Proliferation, Mice
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