title: FGF22 signaling regulates synapse formation during post-injury remodeling of the spinal cord.
abstract: The 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.
authors.affiliation: Institute of Clinical Neuroimmunology, Ludwig-Maximilians Universität München, Munich, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Jacobi
authors.affiliation: Institute of Clinical Neuroimmunology, Ludwig-Maximilians Universität München, Munich, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Loy
authors.affiliation: Institute of Clinical Neuroimmunology, Ludwig-Maximilians Universität München, Munich, Germany.
authors.forename: Anja M
authors.initials: AM
authors.lastname: Schmalz
authors.affiliation: Institute of Clinical Neuroimmunology, Ludwig-Maximilians Universität München, Munich, Germany.
authors.forename: Mikael
authors.initials: M
authors.lastname: Hellsten
authors.affiliation: Department of Neurology, F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA Molecular & Behavioral Neuroscience Institute and Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Umemori
authors.affiliation: Institute of Clinical Neuroimmunology, Ludwig-Maximilians Universität München, Munich, Germany Munich Cluster of Systems Neurology (SyNergy), Munich, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Kerschensteiner
authors.affiliation: Institute of Clinical Neuroimmunology, Ludwig-Maximilians Universität München, Munich, Germany Munich Cluster of Systems Neurology (SyNergy), Munich, Germany Florence.Bareyre@med.uni-muenchen.de.
authors.forename: Florence M
authors.initials: FM
authors.lastname: Bareyre
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009416:Nerve Regeneration / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000378:metabolism; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics / Q000378:metabolism; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000503:physiopathology; D013569:Synapses / Q000378:metabolism* / Q000502:physiology
chemical_list: C476387:Fgf22 protein, mouse; D005346:Fibroblast Growth Factors; C496349:Fgfr1 protein, mouse; C496354:Fgfr2 protein, mouse; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2
keywords: axonal remodeling; fibroblast growth factor; functional recovery; spinal cord injury; synapse formation