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

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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.

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

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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.

"This ORCID iD identifies the author of this article:" 0000-0002-3217-895X
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.
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.

"This ORCID iD identifies the author of this article:" 0000-0001-7577-3794
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.

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.

Copyright

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.