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- Title
Plexin-A2 and its ligand, Sema6A, control nucleus-centrosome coupling in migrating granule cells.
- Authors
Renaud, Julie; Kerjan, Géraldine; Sumita, Itsuko; Zagar, Yvrick; Georget, Virginie; Kim, Doyeun; Fouquet, Coralie; Suda, Kazunori; Sanbo, Makoto; Suto, Fumikazu; Ackerman, Susan L; Mitchell, Kevin J; Fujisawa, Hajime; Chédotal, Alain
- Abstract
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.
- Publication
Nature neuroscience, 2008, Vol 11, Issue 4, p440
- ISSN
1097-6256
- Publication type
Journal Article
- DOI
10.1038/nn2064