1. Neuroscience
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Optical control of ERK and AKT signaling promotes axon regeneration and functional recovery of PNS and CNS in Drosophila

  1. Qin Wang
  2. Huaxun Fan
  3. Feng Li
  4. Savanna S Skeeters
  5. Vishnu V Krishnamurthy
  6. Yuanquan Song  Is a corresponding author
  7. Kai Zhang  Is a corresponding author
  1. University of Pennsylvania, United States
  2. University of Illinois at Urbana-Champaign, United States
Research Article
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Cite this article as: eLife 2020;9:e57395 doi: 10.7554/eLife.57395

Abstract

Neuroregeneration is a dynamic process synergizing the functional outcomes of multiple signaling circuits. Channelrhodopsin-based optogenetics shows the feasibility of stimulating neural repair but does not pin down specific signaling cascades. Here, we utilized optogenetic systems, optoRaf and optoAKT, to delineate the contribution of the ERK and AKT signaling pathways to neuroregeneration in live Drosophila larvae. We showed that optoRaf or optoAKT activation not only enhanced axon regeneration in both regeneration-competent and -incompetent sensory neurons in the peripheral nervous system but also allowed temporal tuning and proper guidance of axon regrowth. Furthermore, optoRaf and optoAKT differ in their signaling kinetics during regeneration, showing a gated versus graded response, respectively. Importantly in the central nervous system, their activation promotes axon regrowth and functional recovery of the thermonociceptive behavior. We conclude that non-neuronal optogenetics target damaged neurons and signaling subcircuits, providing a novel strategy in the intervention of neural damage with improved precision.

Article and author information

Author details

  1. Qin Wang

    Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Huaxun Fan

    Biochemistry, University of Illinois at Urbana-Champaign, Urbana, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Feng Li

    Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Savanna S Skeeters

    Biochemistry, University of Illinois at Urbana-Champaign, Urbana, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Vishnu V Krishnamurthy

    Biochemistry, University of Illinois at Urbana-Champaign, Urbana, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9905-5965
  6. Yuanquan Song

    Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, United States
    For correspondence
    songy2@email.chop.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7699-2059
  7. Kai Zhang

    Biochemistry, University of Illinois at Urbana-Champaign, Urbana, United States
    For correspondence
    kaizkaiz@illinois.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6687-4558

Funding

National Institute of General Medical Sciences (R01GM132438)

  • Huaxun Fan
  • Savanna S Skeeters
  • Vishnu V Krishnamurthy
  • Kai Zhang

National Institute of Neurological Disorders and Stroke (1R01NS107392)

  • Qin Wang
  • Feng Li
  • Yuanquan Song

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: The experimental procedures have been approved by the Institutional Biosafety Committee (IBC) at the Children's Hospital of Philadelphia.

Reviewing Editor

  1. Moses V Chao, New York University Langone Medical Center, United States

Publication history

  1. Received: March 30, 2020
  2. Accepted: September 15, 2020
  3. Accepted Manuscript published: October 6, 2020 (version 1)
  4. Version of Record published: October 16, 2020 (version 2)

Copyright

© 2020, Wang 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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