Revisiting the role of Dcc in visual system development with a novel eye clearing method
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.
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
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.
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.
- Carol A Mason, Columbia University, United States
- Received: August 22, 2019
- Accepted: February 24, 2020
- Accepted Manuscript published: February 25, 2020 (version 1)
- Version of Record published: March 9, 2020 (version 2)
© 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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