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FGF 22 signaling regulates synapse formation during post‐injury remodeling of the spinal cord
Author(s) -
Jacobi Anne,
Loy Kristina,
Schmalz Anja M,
Hellsten Mikael,
Umemori Hisashi,
Kerschensteiner Martin,
Bareyre Florence M
Publication year - 2015
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201490578
Subject(s) - biology , synapse , spinal cord injury , microbiology and biotechnology , spinal cord , fibroblast growth factor , signal transduction , neuroscience , neuromuscular junction , synapse formation , receptor , genetics
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 FGF 22 as a key regulator of circuit remodeling in the injured spinal cord. We show that FGF 22 is produced by spinal relay neurons, while its main receptors FGFR 1 and FGFR 2 are expressed by cortical projection neurons. FGF 22 deficiency or the targeted deletion of FGFR 1 and FGFR 2 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 FGF 22 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.