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dc.contributor.authorSchaeffer, Julia
dc.contributor.authorTannahill, David
dc.contributor.authorCioni, Jean-Michel
dc.contributor.authorRowlands, Dáire
dc.contributor.authorKeynes, Roger
dc.date.accessioned2018-11-01T14:02:02Z
dc.date.available2018-11-01T14:02:02Z
dc.date.issued2018-10-01
dc.identifier.issn0012-1606
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/284479
dc.description.abstractDuring amniote peripheral nervous system development, segmentation ensures the correct patterning of the spinal nerves relative to the vertebral column. Along the antero-posterior (rostro-caudal) axis, each somite-derived posterior half-sclerotome expresses repellent molecules to restrict axon growth and neural crest migration to the permissive anterior half-segment. To identify novel regulators of spinal nerve patterning, we investigated the differential gene expression of anterior and posterior half-sclerotomes in the chick embryo by RNA-sequencing. Several genes encoding extracellular matrix proteins were found to be enriched in either anterior (e.g. Tenascin-C, Laminin alpha 4) or posterior (e.g. Fibulin-2, Fibromodulin, Collagen VI alpha 2) half-sclerotomes. Among them, the extracellular matrix protein Fibulin-2 was found specifically restricted to the posterior half-sclerotome. By using in ovo ectopic expression in chick somites, we found that Fibulin-2 modulates spinal axon growth trajectories in vivo. While no intrinsic axon repellent activity of Fibulin-2 was found, we showed that it enhances the growth cone repulsive activity of Semaphorin 3A in vitro. Some molecules regulating axon growth during development are found to be upregulated in the adult central nervous system (CNS) following traumatic injury. Here, we found increased Fibulin-2 protein levels in reactive astrocytes at the lesion site of a mouse model of CNS injury. Together, these results suggest that the developing vertebral column and the adult CNS share molecular features that control axon growth and plasticity, which may open up the possibility for the identification of novel therapeutic targets for brain and spinal cord injury.
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherElsevier BV
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectSpinal Cord
dc.subjectAstrocytes
dc.subjectAxons
dc.subjectSpinal Nerves
dc.subjectExtracellular Matrix
dc.subjectChick Embryo
dc.subjectSomites
dc.subjectNeural Crest
dc.subjectAnimals
dc.subjectMice
dc.subjectCalcium-Binding Proteins
dc.subjectSemaphorin-3A
dc.subjectExtracellular Matrix Proteins
dc.subjectCell Differentiation
dc.titleIdentification of the extracellular matrix protein Fibulin-2 as a regulator of spinal nerve organization.
dc.typeArticle
prism.endingPage114
prism.issueIdentifier1
prism.publicationDate2018
prism.publicationNameDev Biol
prism.startingPage101
prism.volume442
dc.identifier.doi10.17863/CAM.31855
dcterms.dateAccepted2018-06-19
rioxxterms.versionofrecord10.1016/j.ydbio.2018.06.014
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2018-10
dc.contributor.orcidTannahill, David [0000-0002-3811-6864]
dc.contributor.orcidKeynes, Roger [0000-0002-1557-7684]
dc.identifier.eissn1095-564X
rioxxterms.typeJournal Article/Review
pubs.funder-project-idSpinal Research (ISRT) (Nathalie Rose Studentship)
pubs.funder-project-idRosetrees Trust (JS16/A411)
pubs.funder-project-idRosetrees Trust (A1047)
pubs.funder-project-idCancer Research UK (CB4330)


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Attribution-NonCommercial-NoDerivatives 4.0 International
Except where otherwise noted, this item's licence is described as Attribution-NonCommercial-NoDerivatives 4.0 International