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dc.contributor.authorMITCHELL, KEVINen
dc.date.accessioned2010-08-17T16:03:58Z
dc.date.available2010-08-17T16:03:58Z
dc.date.issued2010en
dc.date.submitted2010en
dc.identifier.citationTawarayama H, Yoshida Y, Suto F, Mitchell KJ, Fujisawa H., Roles of Semaphorin-6B and Plexin-A2 in Lamina-Restricted Projection of Hippocampal Mossy Fibers., Journal of Neuroscience, 30, 20, 2010, 7049-7060en
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/40481
dc.descriptionPUBLISHEDen
dc.descriptionPMID: 20484647en
dc.description.abstractHippocampal mossy fibers project preferentially to the proximal-most lamina of the suprapyramidal region of CA3, the stratum lucidum, and proximal-most parts of the infrapyrmidal region of CA3c. Molecular mechanisms that govern the lamina-restricted projection of mossy fibers, however, have not been fully understood. We previously studied functions of neural repellent Semaphorin-6A (Sema6A), a class 6 transmembrane semaphorin, and its receptors, plexin-A2 (PlxnA2) and PlxnA4, in mossy fiber projection and have proposed that PlxnA4-expressing mossy fibers are principally prevented from entering the Sema6A-expressing suprapyramidal and infrapyramidal regions of CA3 but are permitted to grow into proximal parts of the regions, where repulsive activity of Sema6A is competitively suppressed by PlxnA2 (Suto et al., 2007). In the present study we demonstrate that Sema6B, another class 6 transmembrane semaphorin, is expressed in CA3 and repels mossy fibers in a PlxnA4-dependent manner in vitro. In Sema6B-deficient mice several mossy fibers aberrantly project to the stratum radiatum and the stratum oriens. The number of aberrant mossy fibers is increased in Sema6A;Sema6B double knock-out mice, indicating that Sema6A and Sema6B function additively to regulate proper projection of mossy fibers. PlxnA2 does not suppress the Sema6B response, but itself promotes growth of mossy fibers. Based on these results, we propose that the balance between mossy fiber repulsion by Sema6A and Sema6B and attraction by PlxnA2 and unknown molecule(s) prescribes the areas permissive for mossy fibers to innervate.en
dc.description.sponsorshipThis work was supported by Grants-in-Aid from the Ministry of Education, Science, Sports, and Culture of Japan Ministry of Education (H.F.), grants from the 21 st Century COE Program (H.T. and H.F.), Grant-in-Aid for Young Scientists (B) and CREST (Core Research for Evolutional Science and Technology) of Japan Science and Technology Agency (F.S.), National Institutes of Health Grant RO1 NS065048 (Y.Y.), and a Health Research Board Project Grant (K.J.M.). Sema6B mutant mice were generated in, and generously provided by the Dr. T.M. Jessell Laboratory, at Columbia University (New York, NY). We also thank Drs. M. Mendelsohn, J. Kirkland, and B. Han (Columbia University) in the generation of the Sema6B mutant mice, and Dr. J. Miyazaki (Osaka University, Suita, Japan) for pCAGGS expression vector.en
dc.format.extent7049-7060en
dc.language.isoenen
dc.relation.ispartofseriesJournal of Neuroscienceen
dc.relation.ispartofseries30en
dc.relation.ispartofseries20en
dc.rightsYen
dc.subjectGenetics
dc.titleRoles of Semaphorin-6B and Plexin-A2 in Lamina-Restricted Projection of Hippocampal Mossy Fibers.en
dc.typeJournal Articleen
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/kemitcheen
dc.identifier.rssinternalid66740en
dc.identifier.rssurihttp://dx.doi.org/10.1523/JNEUROSCI.0073-10.2010en


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