Rod nuclear architecture determines contrast transmission of the retina and behavioral sensitivity in mice

  1. Kaushikaram Subramanian
  2. Martin Weigert
  3. Oliver Borsch
  4. Heike Petzold
  5. Alfonso Garcia-Ulloa
  6. Eugene W Myers
  7. Marius Ader
  8. Irina Solovei
  9. Moritz Kreysing  Is a corresponding author
  1. Max Planck Institute of Molecular Cell Biology and Genetics, Germany
  2. Technische Universität Dresden, Germany
  3. Ludwig Maximilians Universität, Germany

Abstract

Rod photoreceptors of nocturnal mammals display a striking inversion of nuclear architecture, which has been proposed as an evolutionary adaptation to dark environments. However, the nature of visual benefits and the underlying mechanisms remains unclear. It is widely assumed that improvements in nocturnal vision would depend on maximization of photon capture at the expense of image detail. Here we show that retinal optical quality improves 2-fold during terminal development, and that this enhancement is caused by nuclear inversion. We further demonstrate that improved retinal contrast transmission, rather than photon-budget or resolution, enhances scotopic contrast sensitivity by 18-27%, and improves motion detection capabilities up to 10-fold in dim environments. Our findings therefore add functional significance to a prominent exception of nuclear organization and establish retinal contrast transmission as a decisive determinant of mammalian visual perception.

Data availability

Data and specifications of simulations supporting the findings of this study are available via https://owncloud.mpi-cbg.de/index.php/s/SaCJjsMCfyOAaTb . The biobeam software is available publicly from: https://maweigert.github.io/biobeam

Article and author information

Author details

  1. Kaushikaram Subramanian

    Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Martin Weigert

    Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Oliver Borsch

    Center for Regenerative Therapies, Technische Universität Dresden, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Heike Petzold

    Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Alfonso Garcia-Ulloa

    Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Eugene W Myers

    Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  7. Marius Ader

    Center for Regenerative Therapies, Technische Universität Dresden, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9467-7677
  8. Irina Solovei

    Biozentrum, Ludwig Maximilians Universität, München, Germany
    Competing interests
    The authors declare that no competing interests exist.
  9. Moritz Kreysing

    Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    For correspondence
    kreysing@mpi-cbg.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7432-3871

Funding

Max-Planck-Gesellschaft

  • Kaushikaram Subramanian
  • Martin Weigert
  • Heike Petzold
  • Alfonso Garcia-Ulloa
  • Eugene W Myers
  • Moritz Kreysing

Technische Universität Dresden

  • Oliver Borsch
  • Marius Ader

Deutsche Forschungsgemeinschaft (AD375/6-1)

  • Oliver Borsch
  • Marius Ader

Bundesministerium für Bildung und Forschung (031L0044)

  • Kaushikaram Subramanian
  • Eugene W Myers
  • Moritz Kreysing

Deutsche Forschungsgemeinschaft (SO1054/3)

  • Irina Solovei

Deutsche Forschungsgemeinschaft (FZT111)

  • Oliver Borsch
  • Marius Ader

Deutsche Forschungsgemeinschaft (EXC68)

  • Oliver Borsch
  • Marius Ader

Deutsche Forschungsgemeinschaft (SFB1064)

  • Irina Solovei

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

Ethics

Animal experimentation: "All animal studies were performed in accordance with European and German animal welfare legislation (Tierschutzgesetz), the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research, and the NIH Guide for the care and use of laboratory work in strict pathogen-free conditions in the animal facilities of the Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany and the Center for Regenerative Therapies Dresden, Germany. Protocols were approved by the Institutional Animal Welfare Officer (Tierschutzbeauftragter) and the ethics committee of the TU Dresden. Necessary licenses 24-9168.24-9/2012-1, DD24.1-5131/451/8 and TVV 16/2018 (DD24-5131/354/19) were obtained from the regional Ethical Commission for Animal Experimentation of Dresden, Germany (Tierversuchskommission, Landesdirektion Sachsen)"

Reviewing Editor

  1. Jeremy Nathans, Johns Hopkins University School of Medicine, United States

Version history

  1. Received: June 20, 2019
  2. Accepted: December 11, 2019
  3. Accepted Manuscript published: December 11, 2019 (version 1)
  4. Version of Record published: January 21, 2020 (version 2)

Copyright

© 2019, Subramanian 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

  • 2,442
    Page views
  • 325
    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. Kaushikaram Subramanian
  2. Martin Weigert
  3. Oliver Borsch
  4. Heike Petzold
  5. Alfonso Garcia-Ulloa
  6. Eugene W Myers
  7. Marius Ader
  8. Irina Solovei
  9. Moritz Kreysing
(2019)
Rod nuclear architecture determines contrast transmission of the retina and behavioral sensitivity in mice
eLife 8:e49542.
https://doi.org/10.7554/eLife.49542

Further reading

    1. Cell Biology
    2. Developmental Biology
    Simon Schneider, Andjela Kovacevic ... Hubert Schorle
    Research Article

    Cylicins are testis-specific proteins, which are exclusively expressed during spermiogenesis. In mice and humans, two Cylicins, the gonosomal X-linked Cylicin 1 (Cylc1/CYLC1) and the autosomal Cylicin 2 (Cylc2/CYLC2) genes, have been identified. Cylicins are cytoskeletal proteins with an overall positive charge due to lysine-rich repeats. While Cylicins have been localized in the acrosomal region of round spermatids, they resemble a major component of the calyx within the perinuclear theca at the posterior part of mature sperm nuclei. However, the role of Cylicins during spermiogenesis has not yet been investigated. Here, we applied CRISPR/Cas9-mediated gene editing in zygotes to establish Cylc1- and Cylc2-deficient mouse lines as a model to study the function of these proteins. Cylc1 deficiency resulted in male subfertility, whereas Cylc2-/-, Cylc1-/yCylc2+/-, and Cylc1-/yCylc2-/- males were infertile. Phenotypical characterization revealed that loss of Cylicins prevents proper calyx assembly during spermiogenesis. This results in decreased epididymal sperm counts, impaired shedding of excess cytoplasm, and severe structural malformations, ultimately resulting in impaired sperm motility. Furthermore, exome sequencing identified an infertile man with a hemizygous variant in CYLC1 and a heterozygous variant in CYLC2, displaying morphological abnormalities of the sperm including the absence of the acrosome. Thus, our study highlights the relevance and importance of Cylicins for spermiogenic remodeling and male fertility in human and mouse, and provides the basis for further studies on unraveling the complex molecular interactions between perinuclear theca proteins required during spermiogenesis.

    1. Cell Biology
    2. Structural Biology and Molecular Biophysics
    Bronwyn A Lucas, Benjamin A Himes, Nikolaus Grigorieff
    Research Advance

    Previously we showed that 2D template matching (2DTM) can be used to localize macromolecular complexes in images recorded by cryogenic electron microscopy (cryo-EM) with high precision, even in the presence of noise and cellular background (Lucas et al., 2021; Lucas et al., 2022). Here, we show that once localized, these particles may be averaged together to generate high-resolution 3D reconstructions. However, regions included in the template may suffer from template bias, leading to inflated resolution estimates and making the interpretation of high-resolution features unreliable. We evaluate conditions that minimize template bias while retaining the benefits of high-precision localization, and we show that molecular features not present in the template can be reconstructed at high resolution from targets found by 2DTM, extending prior work at low-resolution. Moreover, we present a quantitative metric for template bias to aid the interpretation of 3D reconstructions calculated with particles localized using high-resolution templates and fine angular sampling.