1. Developmental Biology
  2. Neuroscience

Retrograde fibroblast growth factor 22 (FGF22) signaling regulates insulin-like growth factor 2 (IGF2) expression for activity-dependent synapse stabilization in the mammalian brain

  1. Akiko Terauchi
  2. Erin M Johnson-Venkatesh
  3. Brenna Bullock
  4. Maria Lehtinen
  5. Hisashi Umemori  Is a corresponding author
  1. Harvard Medical School, United States
https://doi.org/10.7554/eLife.12151
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Cite this article
  1. Akiko Terauchi
  2. Erin M Johnson-Venkatesh
  3. Brenna Bullock
  4. Maria Lehtinen
  5. Hisashi Umemori
(2016)
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
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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.

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Author details

  1. Akiko Terauchi

    Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Erin M Johnson-Venkatesh

    Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Brenna Bullock

    Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Maria Lehtinen

    Department of Pathology, F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Hisashi Umemori

    Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, United States
    For correspondence
    hisashi.umemori@childrens.harvard.edu
    Competing interests
    The authors declare that no competing interests exist.

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).

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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  1. Akiko Terauchi
  2. Erin M Johnson-Venkatesh
  3. Brenna Bullock
  4. Maria Lehtinen
  5. Hisashi Umemori
(2016)
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

Share this article

https://doi.org/10.7554/eLife.12151

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