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FGF22 signaling regulates synapse formation during post‐injury remodeling of the spinal cord
dc.contributor.authorJacobi, Anneen_US
dc.contributor.authorLoy, Kristinaen_US
dc.contributor.authorSchmalz, Anja Men_US
dc.contributor.authorHellsten, Mikaelen_US
dc.contributor.authorUmemori, Hisashien_US
dc.contributor.authorKerschensteiner, Martinen_US
dc.contributor.authorBareyre, Florence Men_US
dc.date.accessioned2015-06-01T18:51:33Z
dc.date.available2016-06-01T20:54:35Zen
dc.date.issued2015-05-05en_US
dc.identifier.citationJacobi, Anne; Loy, Kristina; Schmalz, Anja M; Hellsten, Mikael; Umemori, Hisashi; Kerschensteiner, Martin; Bareyre, Florence M (2015). "FGF22 signaling regulates synapse formation during post‐injury remodeling of the spinal cord." The EMBO Journal 34(9): 1231-1243.en_US
dc.identifier.issn0261-4189en_US
dc.identifier.issn1460-2075en_US
dc.identifier.urihttps://hdl.handle.net/2027.42/111756
dc.description.abstractThe remodeling of axonal circuits after injury requires the formation of new synaptic contacts to enable functional recovery. Which molecular signals initiate such axonal and synaptic reorganisation in the adult central nervous system is currently unknown. Here, we identify FGF22 as a key regulator of circuit remodeling in the injured spinal cord. We show that FGF22 is produced by spinal relay neurons, while its main receptors FGFR1 and FGFR2 are expressed by cortical projection neurons. FGF22 deficiency or the targeted deletion of FGFR1 and FGFR2 in the hindlimb motor cortex limits the formation of new synapses between corticospinal collaterals and relay neurons, delays their molecular maturation, and impedes functional recovery in a mouse model of spinal cord injury. These results establish FGF22 as a synaptogenic mediator in the adult nervous system and a crucial regulator of synapse formation and maturation during post‐injury remodeling in the spinal cord.SynopsisFollowing spinal cord injury, transected projections form detour circuits that circumvent the lesion and contribute to functional recovery. The formation of new synaptic contacts is a crucial step of the process, but its molecular regulation is currently not understood. Members of the FGF family can promote synapse formation during nervous system development, suggesting that they might have a similar function in the injured adult CNS. Here, we show that:FGF22 and FGF22 receptors are expressed in the adult nervous system.FGF22 deficiency or deletion of FGF22 receptors restricts the formation and maturation of new synapses in the injured spinal cord.Genetic disruption of FGF22 signaling impedes spontaneous functional recovery following spinal cord injury.FGF22 is a synaptogenic mediator in the adult nervous system and promotes synaptic plasticity and circuit remodeling in a mouse model of spinal cord injury.en_US
dc.publisherWiley Periodicals, Inc.en_US
dc.subject.otherfibroblast growth factoren_US
dc.subject.otherspinal cord injuryen_US
dc.subject.otheraxonal remodelingen_US
dc.subject.otherfunctional recoveryen_US
dc.subject.othersynapse formationen_US
dc.titleFGF22 signaling regulates synapse formation during post‐injury remodeling of the spinal corden_US
dc.typeArticleen_US
dc.rights.robotsIndexNoFollowen_US
dc.subject.hlbsecondlevelMolecular, Cellular and Developmental Biologyen_US
dc.subject.hlbtoplevelHealth Sciencesen_US
dc.description.peerreviewedPeer Revieweden_US
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/111756/1/embj201490578-sup-0001-Suppl_Info.pdf
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/111756/2/embj201490578.pdf
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/111756/3/embj201490578.reviewer_comments.pdf
dc.identifier.doi10.15252/embj.201490578en_US
dc.identifier.sourceThe EMBO Journalen_US
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dc.owningcollnameInterdisciplinary and Peer-Reviewed


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