The formation of the light-sensing compartment of cone photoreceptors coincides with a transcriptional switch

  1. Janine M Daum
  2. Özkan Keles
  3. Sjoerd J B Holwerda
  4. Hubertus Kohler
  5. Filippo M Rijli
  6. Michael Stadler  Is a corresponding author
  7. Botond Roska  Is a corresponding author
  1. Friedrich Miescher Institute for Biomedical Research, Switzerland

Abstract

High-resolution daylight vision is mediated by cone photoreceptors. The molecular program responsible for the formation of their light sensor, the outer segment, is not well understood. We correlated daily changes in ultrastructure and gene expression in postmitotic mouse cones, between birth and eye opening, using serial block-face electron microscopy (EM) and RNA sequencing. Outer segments appeared rapidly at postnatal day six and their appearance coincided with a switch in gene expression. The switch affected over 14% of all expressed genes. Genes that switched off were rich in transcription factors and neurogenic genes. Those that switched on contained genes relevant for cone function. Chromatin rearrangements in enhancer regions occurred before the switch was completed, but not after. We provide a resource comprised of correlated EM, RNAseq, and ATACseq data, showing that the growth of a key compartment of a postmitotic cell involves an extensive switch in gene expression and chromatin accessibility.

Data availability

The following data sets were generated

Article and author information

Author details

  1. Janine M Daum

    Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  2. Özkan Keles

    Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  3. Sjoerd J B Holwerda

    Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  4. Hubertus Kohler

    Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  5. Filippo M Rijli

    Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0515-0182
  6. Michael Stadler

    Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
    For correspondence
    michael.stadler@fmi.ch
    Competing interests
    The authors declare that no competing interests exist.
  7. Botond Roska

    Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
    For correspondence
    botond.roska@fmi.ch
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9559-1450

Funding

Swiss National Science Foundation (3100330B_163457)

  • Botond Roska

European Research Council (669157)

  • Botond Roska

Swiss Natiional Science Foundation (CRSII3_141801)

  • Botond Roska

European Research Council (RETMUS)

  • Botond Roska

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

Ethics

Animal experimentation: Animal procedures were done in accordance with standard ethical guidelines (European Communities Guidelines on the Care and Use of Laboratory Animals, 86/609/EEC) and were approved by the Veterinary Department of the Canton of Basel-Stadt.

Reviewing Editor

  1. Eve Marder, Brandeis University, United States

Publication history

  1. Received: August 22, 2017
  2. Accepted: November 3, 2017
  3. Accepted Manuscript published: November 6, 2017 (version 1)
  4. Version of Record published: November 14, 2017 (version 2)

Copyright

© 2017, Daum 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

  • 1,721
    Page views
  • 347
    Downloads
  • 17
    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. Janine M Daum
  2. Özkan Keles
  3. Sjoerd J B Holwerda
  4. Hubertus Kohler
  5. Filippo M Rijli
  6. Michael Stadler
  7. Botond Roska
(2017)
The formation of the light-sensing compartment of cone photoreceptors coincides with a transcriptional switch
eLife 6:e31437.
https://doi.org/10.7554/eLife.31437

Further reading

    1. Computational and Systems Biology
    Zhuang Liu et al.
    Research Article Updated

    MicroRNAs (miR), as important epigenetic control factors, reportedly regulate wound repair. However, our insufficient knowledge of clinically relevant miRs hinders their potential therapeutic use. For this, we performed paired small and long RNA-sequencing and integrative omics analysis in human tissue samples, including matched skin and acute wounds collected at each healing stage and chronic nonhealing venous ulcers (VUs). On the basis of the findings, we developed a compendium (https://www.xulandenlab.com/humanwounds-mirna-mrna), which will be an open, comprehensive resource to broadly aid wound healing research. With this first clinical, wound-centric resource of miRs and mRNAs, we identified 17 pathologically relevant miRs that exhibited abnormal VU expression and displayed their targets enriched explicitly in the VU gene signature. Intermeshing regulatory networks controlled by these miRs revealed their high cooperativity in contributing to chronic wound pathology characterized by persistent inflammation and proliferative phase initiation failure. Furthermore, we demonstrated that miR-34a, miR-424, and miR-516, upregulated in VU, cooperatively suppressed keratinocyte migration and growth while promoting inflammatory response. By combining miR expression patterns with their specific target gene expression context, we identified miRs highly relevant to VU pathology. Our study opens the possibility of developing innovative wound treatment that targets pathologically relevant cooperating miRs to attain higher therapeutic efficacy and specificity.

    1. Computational and Systems Biology
    2. Neuroscience
    Vasileios Dimakopoulos et al.
    Research Article

    The maintenance of items in working memory (WM) relies on a widespread network of cortical areas and hippocampus where synchronization between electrophysiological recordings reflects functional coupling. We investigated the direction of information flow between auditory cortex and hippocampus while participants heard and then mentally replayed strings of letters in WM by activating their phonological loop. We recorded local field potentials from the hippocampus, reconstructed beamforming sources of scalp EEG, and – additionally in four participants – recorded from subdural cortical electrodes. When analyzing Granger causality, the information flow was from auditory cortex to hippocampus with a peak in the [4 8] Hz range while participants heard the letters. This flow was subsequently reversed during maintenance while participants maintained the letters in memory. The functional interaction between hippocampus and the cortex and the reversal of information flow provide a physiological basis for the encoding of memory items and their active replay during maintenance.