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Plexin-A2 and its ligand, Sema6A, control nucleus-centrosome coupling in migrating granule cells.

During their migration, cerebellar granule cells switch from a tangential to a radial mode of migration. We have previously demonstrated that this involves the transmembrane semaphorin Sema6A. We show here that plexin-A2 is the receptor that controls Sema6A function in migrating granule cells. In plexin-A2-deficient (Plxna2(-/-)) mice, which were generated by homologous recombination, many granule cells remained in the molecular layer, as we saw in Sema6a mutants. A similar phenotype was observed in mutant mice that were generated by mutagenesis with N-ethyl-N-nitrosourea and had a single amino-acid substitution in the semaphorin domain of plexin-A2. We found that this mutation abolished the ability of Sema6A to bind to plexin-A2. Mouse chimera studies further suggested that plexin-A2 acts in a cell-autonomous manner. We also provide genetic evidence for a ligand-receptor relationship between Sema6A and plexin-A2 in this system. Using time-lapse video microscopy, we found that centrosome-nucleus coupling and coordinated motility were strongly perturbed in Sema6a(-/-) and Plxna2(-/-) granule cells. This suggests that semaphorin-plexin signaling modulates cell migration by controlling centrosome positioning.

Pubmed ID: 18327254

Authors

  • Renaud J
  • Kerjan G
  • Sumita I
  • Zagar Y
  • Georget V
  • Kim D
  • Fouquet C
  • Suda K
  • Sanbo M
  • Suto F
  • Ackerman SL
  • Mitchell KJ
  • Fujisawa H
  • Ch├ędotal A

Journal

Nature neuroscience

Publication Data

April 27, 2008

Associated Grants

  • Agency: NINDS NIH HHS, Id: NS041215
  • Agency: NINDS NIH HHS, Id: NS35900
  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

  • Animals
  • Cell Movement
  • Cell Nucleus
  • Cells, Cultured
  • Centrosome
  • Cerebellum
  • Gene Expression Regulation, Developmental
  • In Vitro Techniques
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nerve Tissue Proteins
  • Neurons
  • Receptors, Cell Surface
  • Semaphorins