title: Retrograde fibroblast growth factor 22 (FGF22) signaling regulates insulin-like growth factor 2 (IGF2) expression for activity-dependent synapse stabilization in the mammalian brain.
abstract: Communication between pre- and postsynaptic cells promotes the initial organization of synaptic specializations, but subsequent synaptic stabilization requires transcriptional regulation. Here we show that fibroblast growth factor 22 (FGF22), a target-derived presynaptic organizer in the mouse hippocampus, induces the expression of insulin-like growth factor 2 (IGF2) for the stabilization of presynaptic terminals. FGF22 is released from CA3 pyramidal neurons and organizes the differentiation of excitatory nerve terminals formed onto them. Local application of FGF22 on the axons of dentate granule cells (DGCs), which are presynaptic to CA3 pyramidal neurons, induces IGF2 in the DGCs. IGF2, in turn, localizes to DGC presynaptic terminals and stabilizes them in an activity-dependent manner. IGF2 application rescues presynaptic defects of Fgf22(-/-) cultures. IGF2 is dispensable for the initial presynaptic differentiation, but is required for the following presynaptic stabilization both in vitro and in vivo. These results reveal a novel feedback signal that is critical for the activity-dependent stabilization of presynaptic terminals in the mammalian hippocampus.
authors.affiliation: Department of Neurology, F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, United States.
authors.forename: Akiko
authors.initials: A
authors.lastname: Terauchi
authors.affiliation: Department of Neurology, F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, United States.
authors.forename: Erin M
authors.initials: EM
authors.lastname: Johnson-Venkatesh
authors.affiliation: Department of Neurology, F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, United States.
authors.forename: Brenna
authors.initials: B
authors.lastname: Bullock
authors.affiliation: Department of Pathology, F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, United States.
authors.forename: Maria K
authors.initials: MK
authors.lastname: Lehtinen
authors.affiliation: Department of Neurology, F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, United States.
authors.forename: Hisashi
authors.identifier: 0000-0001-7198-2062
authors.initials: H
authors.lastname: Umemori
mesh_terms: D000818:Animals; D002450:Cell Communication; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000502:physiology*; D007335:Insulin-Like Growth Factor II / Q000096:biosynthesis*; D051379:Mice; D009474:Neurons / Q000502:physiology*; D013569:Synapses / Q000502:physiology*
chemical_list: C476387:Fgf22 protein, mouse; C513121:IGF2 protein, mouse; D005346:Fibroblast Growth Factors; D007335:Insulin-Like Growth Factor II
keywords: developmental biology; feedback signaling; hippocampus; mouse; neural activity; neuroscience; presynaptic organizer; stem cells; synaptic stabilization; transcriptional regulation