FGF22 signaling regulates synapse formation during post‐injury remodeling of the spinal cord |
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| Authors: | Anne Jacobi Kristina Loy Anja M Schmalz Mikael Hellsten Hisashi Umemori Martin Kerschensteiner Florence M Bareyre |
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| Institution: | 1.Institute of Clinical Neuroimmunology, Ludwig-Maximilians Universität München, Munich, Germany;2.Department of Neurology, F.M. Kirby Neurobiology Center, Boston Children''s Hospital, Harvard Medical School, Boston, MA, USA;3.Molecular & Behavioral Neuroscience Institute and Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI, USA;4.Munich Cluster of Systems Neurology (SyNergy), Munich, Germany |
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| 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. |
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| Keywords: | axonal remodeling fibroblast growth factor functional recovery spinal cord injury synapse formation |
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