Drosophila Hedgehog can act as a morphogen in the absence of regulated Ci processing

  1. Jamie C Little
  2. Elisa Garcia-Garcia
  3. Amanda Sul
  4. Daniel Kalderon  Is a corresponding author
  1. Columbia University, United States

Abstract

Extracellular Hedgehog (Hh) proteins induce transcriptional changes in target cells by inhibiting the proteolytic processing of full-length Drosophila Ci or mammalian Gli proteins to nuclear transcriptional repressors and by activating the full-length Ci or Gli proteins. We used Ci variants expressed at physiological levels to investigate the contributions of these mechanisms to dose-dependent Hh signaling in Drosophila wing imaginal discs. Ci variants that cannot be processed supported a normal pattern of graded target gene activation and the development of adults with normal wing morphology, when supplemented by constitutive Ci repressor, showing that Hh can signal normally in the absence of regulated processing. The processing-resistant Ci variants were also significantly activated in the absence of Hh by elimination of Cos2, likely acting through binding the CORD domain of Ci, or PKA, revealing separate inhibitory roles of these two components in addition to their well-established roles in promoting Ci processing.

Data availability

All data reported in this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Jamie C Little

    Biological Sciences, Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Elisa Garcia-Garcia

    Biological Sciences, Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Amanda Sul

    Biological Sciences, Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Daniel Kalderon

    Biological Sciences, Columbia University, New York, United States
    For correspondence
    ddk1@columbia.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2149-0673

Funding

National Institutes of Health (RO1 GM041815)

  • Daniel Kalderon

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

Reviewing Editor

  1. Claude Desplan, New York University, United States

Publication history

  1. Received: July 15, 2020
  2. Accepted: October 20, 2020
  3. Accepted Manuscript published: October 21, 2020 (version 1)
  4. Version of Record published: November 20, 2020 (version 2)

Copyright

© 2020, Little 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. Jamie C Little
  2. Elisa Garcia-Garcia
  3. Amanda Sul
  4. Daniel Kalderon
(2020)
Drosophila Hedgehog can act as a morphogen in the absence of regulated Ci processing
eLife 9:e61083.
https://doi.org/10.7554/eLife.61083

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