Retrograde fibroblast growth factor 22 (FGF22) signaling regulates insulin-like growth factor 2 (IGF2) expression for activity-dependent synapse stabilization in the mammalian brain
- Harvard Medical School, United States
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.
Article and author information
Author details
Reviewing Editor
- Eunjoon Kim, Korea Advanced Institute of Science and Technology, Republic of Korea
Ethics
Animal experimentation: All animal care and use in this study was in accordance with the institutional guidelines and approved by the Institutional Animal Care and Use Committees at Boston Children's Hospital (#13-11-2528) and University of Michigan (#PRO00003549).
Version history
- Received: October 7, 2015
- Accepted: April 14, 2016
- Accepted Manuscript published: April 15, 2016 (version 1)
- Version of Record published: May 16, 2016 (version 2)
Copyright
© 2016, Terauchi et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Retrograde fibroblast growth factor 22 (FGF22) signaling regulates insulin-like growth factor 2 (IGF2) expression for activity-dependent synapse stabilization in the mammalian brain
eLife 5:e12151.
https://doi.org/10.7554/eLife.12151
