Revisiting the role of Dcc in visual system development with a novel eye clearing method

  1. Robin J Vigouroux
  2. Quénol Cesar
  3. Alain Chédotal  Is a corresponding author
  4. Kim Tuyen Nguyen-Ba-Charvet  Is a corresponding author
  1. Sorbonne Université, UPMC Univ Paris 06, INSERM, CNRS, France
  2. Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, France

Abstract

The Deleted in Colorectal Carcinoma (Dcc) receptor plays a critical role in optic nerve development. Whilst Dcc is expressed postnatally in the eye, its function remains unknown as Dcc knockouts die at birth. To circumvent this drawback, we generated an eye-specific Dcc mutant. To study the organization of the retina and visual projections in these mice, we also established EyeDISCO, a novel tissue clearing protocol that removes melanin allowing 3D imaging of whole eyes and visual pathways. We show that in the absence of Dcc, some ganglion cell axons stalled at the optic disc, whereas others perforated the retina, separating photoreceptors from the retinal pigment epithelium. A subset of visual axons entered the CNS, but these projections are perturbed. Moreover, Dcc-deficient retinas displayed a massive postnatal loss of retinal ganglion cells and a large fraction of photoreceptors. Thus, Dcc is essential for the development and maintenance of the retina.

Data availability

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

Article and author information

Author details

  1. Robin J Vigouroux

    Institut de la Vision, Sorbonne Université, UPMC Univ Paris 06, INSERM, CNRS, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3217-895X
  2. Quénol Cesar

    Institut de la Vision, Sorbonne Université, UPMC Univ Paris 06, INSERM, CNRS, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Alain Chédotal

    Institut de la Vision, Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Paris, France
    For correspondence
    alain.chedotal@inserm.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7577-3794
  4. Kim Tuyen Nguyen-Ba-Charvet

    Institut de la Vision, Sorbonne Université, UPMC Univ Paris 06, INSERM, CNRS, Paris, France
    For correspondence
    kim.charvet@inserm.fr
    Competing interests
    The authors declare that no competing interests exist.

Funding

Fondation ARC pour la Recherche sur le Cancer (DOC20190508735)

  • Robin J Vigouroux

Agence Nationale de la Recherche (ANR-11-IDEX-0004-02)

  • Alain Chédotal

Agence Nationale de la Recherche (ANR-10-LABX-65)

  • Alain Chédotal

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

Reviewing Editor

  1. Carol A Mason, Columbia University, United States

Ethics

Animal experimentation: All experiments were designed using the 3R rule: to reduce, refine, and replace the use of animals. All animal procedures were carried out according to approved institutional guidelines (#B-75-12-02) of the Institut de la Vision. The protocol was approved by the Sorbonne University ethic committee (Charles Darwin)(Permit Number: 9571). In cases of animal handling, experiments were performed to minimize animal stress and suffering.

Version history

  1. Received: August 22, 2019
  2. Accepted: February 24, 2020
  3. Accepted Manuscript published: February 25, 2020 (version 1)
  4. Version of Record published: March 9, 2020 (version 2)

Copyright

© 2020, Vigouroux 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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  1. Robin J Vigouroux
  2. Quénol Cesar
  3. Alain Chédotal
  4. Kim Tuyen Nguyen-Ba-Charvet
(2020)
Revisiting the role of Dcc in visual system development with a novel eye clearing method
eLife 9:e51275.
https://doi.org/10.7554/eLife.51275

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https://doi.org/10.7554/eLife.51275

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