Plexin-B2, but not plexin-B1, critically modulates neuronal migration and patterning of the developing nervous system in vivo

Suhua Deng, Alexandra Hirschberg, Thomas Worzfeld, Junia Y. Penachioni, Alexander Korostylev, Jakub M. Swiercz, Peter Vodrazka, Olivier Mauti, Esther T. Stoeckli, Luca Tamagnone, Stefan Offermanns, Rohini Kuner

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)6333-6347
Number of pages15
JournalJournal of Neuroscience
Volume27
Issue number23
DOIs
Publication statusPublished - Jun 6 2007

Fingerprint

Nervous System
Semaphorins
plexin
Cell Movement
Vertebrates
Neural Tube
Organogenesis
Neural Tube Defects
Olfactory Bulb
Dentate Gyrus
Peripheral Nervous System
Actin Cytoskeleton
Knockout Mice
Cerebellum
Cues
Ligands

Keywords

  • Cerebellum
  • Dentate gyrus
  • Granule cell
  • Knock-out mice
  • Rho GTPases
  • Semaphorin

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Deng, S., Hirschberg, A., Worzfeld, T., Penachioni, J. Y., Korostylev, A., Swiercz, J. M., ... Kuner, R. (2007). Plexin-B2, but not plexin-B1, critically modulates neuronal migration and patterning of the developing nervous system in vivo. Journal of Neuroscience, 27(23), 6333-6347. https://doi.org/10.1523/JNEUROSCI.5381-06.2007

Plexin-B2, but not plexin-B1, critically modulates neuronal migration and patterning of the developing nervous system in vivo. / Deng, Suhua; Hirschberg, Alexandra; Worzfeld, Thomas; Penachioni, Junia Y.; Korostylev, Alexander; Swiercz, Jakub M.; Vodrazka, Peter; Mauti, Olivier; Stoeckli, Esther T.; Tamagnone, Luca; Offermanns, Stefan; Kuner, Rohini.

In: Journal of Neuroscience, Vol. 27, No. 23, 06.06.2007, p. 6333-6347.

Research output: Contribution to journalArticle

Deng, S, Hirschberg, A, Worzfeld, T, Penachioni, JY, Korostylev, A, Swiercz, JM, Vodrazka, P, Mauti, O, Stoeckli, ET, Tamagnone, L, Offermanns, S & Kuner, R 2007, 'Plexin-B2, but not plexin-B1, critically modulates neuronal migration and patterning of the developing nervous system in vivo', Journal of Neuroscience, vol. 27, no. 23, pp. 6333-6347. https://doi.org/10.1523/JNEUROSCI.5381-06.2007
Deng, Suhua ; Hirschberg, Alexandra ; Worzfeld, Thomas ; Penachioni, Junia Y. ; Korostylev, Alexander ; Swiercz, Jakub M. ; Vodrazka, Peter ; Mauti, Olivier ; Stoeckli, Esther T. ; Tamagnone, Luca ; Offermanns, Stefan ; Kuner, Rohini. / Plexin-B2, but not plexin-B1, critically modulates neuronal migration and patterning of the developing nervous system in vivo. In: Journal of Neuroscience. 2007 ; Vol. 27, No. 23. pp. 6333-6347.
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