Natural variation in stochastic photoreceptor specification and color preference in Drosophila

  1. Caitlin Anderson
  2. India Reiss
  3. Cyrus Zhou
  4. Annie Cho
  5. Haziq Siddiqi
  6. Benjamin Mormann
  7. Cameron M Avelis
  8. Peter Deford
  9. Alan Bergland
  10. Elijah Roberts
  11. James Taylor
  12. Daniel Vasiliauskas
  13. Robert J Johnston  Is a corresponding author
  1. Johns Hopkins University, United States
  2. New York University, United States
  3. University of Virginia, United States
  4. Université Paris-Saclay, France

Abstract

Each individual perceives the world in a unique way, but little is known about the genetic basis of variation in sensory perception. In the fly eye, the random mosaic of color-detecting R7 photoreceptor subtypes is determined by stochastic ON/OFF expression of the transcription factor Spineless (Ss). In a genome-wide association study, we identified a naturally occurring insertion in a regulatory DNA element in ss that lowers the ratio of SsON to SsOFF cells. This change in photoreceptor fates shifts the innate color preference of flies from green to blue. The genetic variant increases the binding affinity for Klumpfuss (Klu), a zinc finger transcriptional repressor that regulates ss expression. Klu is expressed at intermediate levels to determine the normal ratio of SsON to SsOFF cells. Thus, binding site affinity and transcription factor levels are finely tuned to regulate stochastic expression, setting the ratio of alternative fates and ultimately determining color preference.

Article and author information

Author details

  1. Caitlin Anderson

    Department of Biology, Johns Hopkins University, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. India Reiss

    Department of Biology, Johns Hopkins University, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Cyrus Zhou

    Department of Biology, Johns Hopkins University, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Annie Cho

    Department of Biology, Johns Hopkins University, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Haziq Siddiqi

    Department of Biology, Johns Hopkins University, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Benjamin Mormann

    Department of Biology, New York University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Cameron M Avelis

    Department of Biophysics, Johns Hopkins University, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Peter Deford

    Department of Biology, Johns Hopkins University, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Alan Bergland

    Department of Biology, University of Virginia, Charlottesville, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7145-7575
  10. Elijah Roberts

    Department of Biophysics, Johns Hopkins University, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. James Taylor

    Department of Biology, Johns Hopkins University, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5079-840X
  12. Daniel Vasiliauskas

    Centre National de la Recherche Scientifique-Unité, Université Paris-Saclay, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  13. Robert J Johnston

    Department of Biology, Johns Hopkins University, Baltimore, United States
    For correspondence
    robertjohnston@jhu.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5775-6218

Funding

National Eye Institute (R01EY025598)

  • Robert J Johnston

Pew Charitable Trusts (27373)

  • Robert J Johnston

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

Reviewing Editor

  1. Simon G Sprecher, University of Fribourg, Switzerland

Publication history

  1. Received: June 14, 2017
  2. Accepted: December 15, 2017
  3. Accepted Manuscript published: December 18, 2017 (version 1)
  4. Accepted Manuscript updated: December 22, 2017 (version 2)
  5. Accepted Manuscript updated: December 23, 2017 (version 3)
  6. Version of Record published: December 27, 2017 (version 4)
  7. Version of Record updated: January 12, 2018 (version 5)
  8. Version of Record updated: April 16, 2018 (version 6)

Copyright

© 2017, Anderson 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.

Metrics

  • 3,079
    Page views
  • 395
    Downloads
  • 16
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Caitlin Anderson
  2. India Reiss
  3. Cyrus Zhou
  4. Annie Cho
  5. Haziq Siddiqi
  6. Benjamin Mormann
  7. Cameron M Avelis
  8. Peter Deford
  9. Alan Bergland
  10. Elijah Roberts
  11. James Taylor
  12. Daniel Vasiliauskas
  13. Robert J Johnston
(2017)
Natural variation in stochastic photoreceptor specification and color preference in Drosophila
eLife 6:e29593.
https://doi.org/10.7554/eLife.29593
  1. Further reading

Further reading

    1. Developmental Biology
    2. Neuroscience
    Juan M Angueyra, Vincent P Kunze ... Wei Li
    Tools and Resources

    During development, retinal progenitors navigate a complex landscape of fate decisions to generate the major cell classes necessary for proper vision. Transcriptional regulation is critical to generate diversity within these major cell classes. Here, we aim to provide the resources and techniques required to identify transcription factors necessary to generate and maintain diversity in photoreceptor subtypes, which are critical for vision. First, we generate a key resource: a high-quality and deep transcriptomic profile of each photoreceptor subtype in adult zebrafish. We make this resource openly accessible, easy to explore, and have integrated it with other currently available photoreceptor transcriptomic datasets. Second, using our transcriptomic profiles, we derive an in-depth map of expression of transcription factors in photoreceptors. Third, we use efficient CRISPR-Cas9 based mutagenesis to screen for null phenotypes in F0 larvae (F0 screening) as a fast, efficient, and versatile technique to assess the involvement of candidate transcription factors in the generation of photoreceptor subtypes. We first show that known phenotypes can be easily replicated using this method: loss of S cones in foxq2 mutants and loss of rods in nr2e3 mutants. We then identify novel functions for the transcription factor Tbx2, demonstrating that it plays distinct roles in controlling the generation of all photoreceptor subtypes within the retina. Our study provides a roadmap to discover additional factors involved in this process. Additionally, we explore four transcription factors of unknown function (Skor1a, Sall1a, Lrrfip1a, and Xbp1), and find no evidence for their involvement in the generation of photoreceptor subtypes. This dataset and screening method will be a valuable way to explore the genes involved in many other essential aspects of photoreceptor biology.

    1. Developmental Biology
    Bavat Bornstein, Lia Heinemann-Yerushalmi ... Elazar Zelzer
    Tools and Resources

    The proprioceptive system is essential for the control of coordinated movement, posture and skeletal integrity. The sense of proprioception is produced in the brain using peripheral sensory input from receptors such as the muscle spindle, which detects changes in the length of skeletal muscles. Despite its importance, the molecular composition of the muscle spindle is largely unknown. In this study, we generated comprehensive transcriptomic and proteomic datasets of the entire muscle spindle isolated from the murine deep masseter muscle. We then associated differentially expressed genes with the various tissues composing the spindle using bioinformatic analysis. Immunostaining verified these predictions, thus establishing new markers for the different spindle tissues. Utilizing these markers, we identified the differentiation stages the spindle capsule cells undergo during development. Together, these findings provide comprehensive molecular characterization of the intact spindle as well as new tools to study its development and function in health and disease.