1. Neuroscience
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A low affinity cis-regulatory BMP response element restricts target gene activation to subsets of Drosophila neurons

  1. Anthony JE Berndt
  2. Katerina M Othonos
  3. Tianshun Lian
  4. Stephane Flibotte
  5. Mo Miao
  6. Shamsuddin Buiyan
  7. Raymond Y Cho
  8. Justin S Fong
  9. Seo Am Hur
  10. Paul Pavlidis
  11. Douglas W Allan  Is a corresponding author
  1. University of California San, Diego, United States
  2. University of British Columbia, Canada
Research Article
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Cite this article as: eLife 2020;9:e59650 doi: 10.7554/eLife.59650

Abstract

Retrograde BMP signaling and canonical pMad/Medea-mediated transcription regulates diverse target genes across subsets of Drosophila efferent neurons, to differentiate neuropeptidergic neurons and promote motor neuron terminal maturation. How a common BMP signal regulates diverse target genes across neuronal subsets remains largely unresolved, although available evidence implicates subset-specific transcription factor codes rather than differences in BMP signaling. Here, we examine the cis-regulatory mechanisms restricting BMP-induced FMRFa neuropeptide expression to Tv4 neurons. We find that pMad/Medea bind at an atypical, low affinity motif in the FMRFa enhancer. Converting this motif to high affinity caused ectopic enhancer activity and eliminated Tv4 neuron expression. In silico searches identified additional motif instances functional in other efferent neurons, implicating broader functions for this motif in BMP-dependent enhancer activity. Thus, differential interpretation of a common BMP signal, conferred by low affinity pMad/Medea binding motifs, can contribute to the specification of BMP target genes in efferent neuron subsets.

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All data generated or analysed during this study are included in the manuscript and supporting files

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Author details

  1. Anthony JE Berndt

    Department of Food & Fuel for the 21st Century, University of California San, Diego, San Diego, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0132-7393

  2. Katerina M Othonos

    Cellular and Physiological Sciences, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.

  3. Tianshun Lian

    Cellular and Physiological Sciences, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.

  4. Stephane Flibotte

    UBC/LSI Bioinformatics Facility, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.

  5. Mo Miao

    Cellular and Physiological Sciences, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.

  6. Shamsuddin Buiyan

    Psychiatry, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.

  7. Raymond Y Cho

    Cellular and Physiological Sciences, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.

  8. Justin S Fong

    Cellular and Physiological Sciences, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.

  9. Seo Am Hur

    Cellular and Physiological Sciences, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4163-7182

  10. Paul Pavlidis

    Psychiatry/Michael Smith Laboratories, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0426-5028

  11. Douglas W Allan

    Cellular and Physiological Sciences, University of British Columbia, Vancouver, Canada
    For correspondence
    doug.allan@ubc.ca
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3488-8365

Funding

Canadian Institutes of Health Research (MOP-98011)

  • Douglas W Allan

Canadian Institutes of Health Research (MOP-130517)

  • Douglas W Allan

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

Reviewing Editor

  1. Oliver Hobert, Howard Hughes Medical Institute, Columbia University, United States

Publication history

  1. Received: June 3, 2020
  2. Accepted: October 29, 2020
  3. Accepted Manuscript published: October 30, 2020 (version 1)
  4. Version of Record published: November 16, 2020 (version 2)

Copyright

© 2020, Berndt 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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