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. Paris-Saclay Institute of Neuroscience, Université Paris Sud, Centre National de la Recherche Scientifque, 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

    Paris-Saclay Institute of Neuroscience, Université Paris Sud, Centre National de la Recherche Scientifque, Université Paris-Saclay, Gif-sur-Yvette, 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

  • 2,933
    Page views
  • 367
    Downloads
  • 10
    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

Further reading

    1. Developmental Biology
    Julia Falo-Sanjuan, Sarah Bray
    Research Article

    Cells sense and integrate external information from diverse sources that include mechanical cues. Shaping of tissues during development may thus require coordination between mechanical forces from morphogenesis and cell-cell signalling to confer appropriate changes in gene expression. By live-imaging Notch-induced transcription in real time we have discovered that morphogenetic movements during Drosophila gastrulation bring about an increase in activity-levels of a Notch responsive enhancer. Mutations that disrupt the timing of gastrulation resulted in concomitant delays in transcription up-regulation that correlated with the start of mesoderm invagination. As a similar gastrulation-induced effect was detected when transcription was elicited by the intracellular domain NICD, it cannot be attributed to forces exerted on Notch receptor activation. A Notch independent vnd enhancer also exhibited a modest gastrulation-induced activity increase in the same stripe of cells. Together, these observations argue that gastrulation-associated forces act on the nucleus to modulate transcription levels. This regulation was uncoupled when the complex linking the nucleoskeleton and cytoskeleton (LINC) was disrupted, indicating a likely conduit. We propose that the coupling between tissue level mechanics, arising from gastrulation, and enhancer activity represents a general mechanism for ensuring correct tissue specification during development and that Notch dependent enhancers are highly sensitive to this regulation.

    1. Developmental Biology
    2. Medicine
    Derek C Sung et al.
    Short Report Updated

    During formation of the mammalian placenta, trophoblasts invade the maternal decidua and remodel spiral arteries to bring maternal blood into the placenta. This process, known as endovascular invasion, is thought to involve the adoption of functional characteristics of vascular endothelial cells (ECs) by trophoblasts. The genetic and molecular basis of endovascular invasion remains poorly defined, however, and whether trophoblasts utilize specialized endothelial proteins in an analogous manner to create vascular channels remains untested. Vascular endothelial (VE-)cadherin is a homotypic adhesion protein that is expressed selectively by ECs in which it enables formation of tight vessels and regulation of EC junctions. VE-cadherin is also expressed in invasive trophoblasts and is a prime candidate for a molecular mechanism of endovascular invasion by those cells. Here, we show that VE-cadherin is required for trophoblast migration and endovascular invasion into the maternal decidua in the mouse. VE-cadherin deficiency results in loss of spiral artery remodeling that leads to decreased flow of maternal blood into the placenta, fetal growth restriction, and death. These studies identify a non-endothelial role for VE-cadherin in trophoblasts during placental development and suggest that endothelial proteins may play functionally unique roles in trophoblasts that do not simply mimic those in ECs.