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dc.contributor.authorMITCHELL, KEVINen
dc.contributor.authorLITTLE, GRAHAMen
dc.date.accessioned2010-05-21T15:09:08Z
dc.date.available2010-05-21T15:09:08Z
dc.date.issued2008en
dc.date.submitted2008en
dc.identifier.citationRünker, AE, Little, GE, Suto, F, Fujisawa, H, Mitchell, KJ, Semaphorin-6A controls guidance of corticospinal tract axons at multiple choice points., Neural development, 3, 34, 2008en
dc.identifier.issn1749-8104en
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/39643
dc.descriptionPUBLISHEDen
dc.description.abstractBackground: The trajectory of corticospinal tract (CST) axons from cortex to spinal cord involves a succession of choice points, each of which is controlled by multiple guidance molecules. To assess the involvement of transmembrane semaphorins and their plexin receptors in the guidance of CST axons, we have examined this tract in mutants of Semaphorin-6A (Sema6A), Plexin- A2 (PlxnA2) and Plexin-A4 (PlxnA4). Results: We describe defects in CST guidance in Sema6A mutants at choice points at the midhindbrain boundary (MHB) and in navigation through the pons that dramatically affect how many axons arrive to the hindbrain and spinal cord and result in hypoplasia of the CST. We also observe defects in guidance within the hindbrain where a proportion of axons aberrantly adopt a ventrolateral position and fail to decussate. This function in the hindbrain seems to be mediated by the known Sema6A receptor PlxnA4, which is expressed by CST axons. Guidance at the MHB, however, appears independent of this and of the other known receptor, PlxnA2, and may depend instead on Sema6A expression on CST axons themselves at embryonic stages. Conclusion: These data identify Sema6A as a major contributor to the guidance of CST axons at multiple choice points. They highlight the active control of guidance at the MHB and also implicate the inferior olive as an important structure in the guidance of CST axons within the hindbrain. They also suggest that Sema6A, which is strongly expressed by oligodendrocytes, may affect CST regeneration in adults.en
dc.description.sponsorshipWe are very grateful to Jackie Dolan for technical assistance with genotyping and to her and Mary Phillips for help with mouse breeding. We thank Marc Tessier-Lavigne and colleagues for the gift of Plxn in situ probes and William Snider for the Sema6A probe. We also thank Hwai-Jong Cheng and colleagues for communicating unpublished data and for very useful discussions. We are very grateful to Marius Ader for generous help with microscopy. This work was supported by grants from Science Foundation Ireland (01/F1/B006) to KJM and a postdoctoral fellowship from the Health Research Board to AER (PD/2004/16). GEL has been supported by a Government of Ireland Scholarship, awarded by the Irish Research Council of Science, Engineering and Technology. HF was supported by the 21st Century Centers of Excellence Program and Grants-in-Aid for Scientific Research Japan. FS was supported by grants from CREST of the Japanese Science and Technology Agency.en
dc.language.isoenen
dc.relation.ispartofseriesNeural developmenten
dc.relation.ispartofseries3en
dc.relation.ispartofseries34en
dc.rightsYen
dc.subjectGenetics
dc.titleSemaphorin-6A controls guidance of corticospinal tract axons at multiple choice points.en
dc.typeJournal Articleen
dc.contributor.sponsorScience Foundation Ireland (SFI)en
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/kemitcheen
dc.identifier.rssinternalid59457en
dc.identifier.doihttp://dx.doi.org/10.1186/1749-8104-3-34en
dc.identifier.rssurihttp://www.neuraldevelopment.com/content/3/1/34en


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