1. Neuroscience
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A versatile genetic tool for post-translational control of gene expression in Drosophila melanogaster

  1. Sachin Sethi
  2. Jing W Wang  Is a corresponding author
  1. University of California, San Diego, United States
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Cite this article as: eLife 2017;6:e30327 doi: 10.7554/eLife.30327


Several techniques have been developed to manipulate gene expression temporally in intact neural circuits. However, the applicability of current tools developed for in vivo studies in Drosophila is limited by their incompatibility with existing GAL4 lines and side effects on physiology and behavior. To circumvent these limitations, we adopted a strategy to reversibly regulate protein degradation with a small molecule by using a destabilizing domain (DD). We show that this system is effective across different tissues and developmental stages. We further show that this system can be used to control in vivo gene expression levels with low background, large dynamic range, and in a reversible manner without detectable side effects on the lifespan or behavior of the animal. Additionally, we engineered tools for chemically controlling gene expression (GAL80-DD) and recombination (FLP-DD). We demonstrate the applicability of this technology in manipulating neuronal activity and for high-efficiency sparse labeling of neuronal populations.

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Author details

  1. Sachin Sethi

    Neurobiology Section, Division of Biological Sciences, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Jing W Wang

    Neurobiology Section, Division of Biological Sciences, University of California, San Diego, La Jolla, United States
    For correspondence
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6291-5802


National Institute on Deafness and Other Communication Disorders (R01DC009597)

  • Jing W Wang

National Institute of Diabetes and Digestive and Kidney Diseases (R01DK092640)

  • Jing W Wang

National Institute of Mental Health (R21MH106958)

  • Jing W Wang

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

Reviewing Editor

  1. Mani Ramaswami, Trinity College Dublin, Ireland

Publication history

  1. Received: July 12, 2017
  2. Accepted: November 14, 2017
  3. Accepted Manuscript published: November 15, 2017 (version 1)
  4. Version of Record published: November 27, 2017 (version 2)


© 2017, Sethi & Wang

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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