| Autor: |
Suhua Deng, 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 |
| Předmět: |
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| Zdroj: |
Journal of Neuroscience; 6/6/2007, Vol. 27 Issue 23, p6333-6347, 15p, 9 Diagrams, 1 Graph |
| Abstrakt: |
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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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