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Development. 2018 Nov 2;145(21). pii: dev163212. doi: 10.1242/dev.163212.

Activation of Wnt signaling reduces ipsilaterally projecting retinal ganglion cells in pigmented retina.

Author information

1
Department of Pathology and Cell Biology, Columbia University, College of Physicians and Surgeons, New York, NY 10027, USA.
2
Department of Ophthalmology, Columbia University, College of Physicians and Surgeons, New York, NY 10027, USA.
3
Department of Neuroscience, Columbia University, New York, NY 10027, USA.
4
Department of Pathology and Cell Biology, Columbia University, College of Physicians and Surgeons, New York, NY 10027, USA cam4@columbia.edu.
5
Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA.

Abstract

In mammalian albinism, disrupted melanogenesis in the retinal pigment epithelium (RPE) is associated with fewer retinal ganglion cells (RGCs) projecting ipsilaterally to the brain, resulting in numerous abnormalities in the retina and visual pathway, especially binocular vision. To further understand the molecular link between disrupted RPE and a reduced ipsilateral RGC projection in albinism, we compared gene expression in the embryonic albino and pigmented mouse RPE. We found that the Wnt pathway, which directs peripheral retinal differentiation and, generally, cell proliferation, is dysregulated in the albino RPE. Wnt2b expression is expanded in the albino RPE compared with the pigmented RPE, and the expanded region adjoins the site of ipsilateral RGC neurogenesis and settling. Pharmacological activation of Wnt signaling in pigmented mice by lithium (Li+) treatment in vivo reduces the number of Zic2-positive RGCs, which are normally fated to project ipsilaterally, to numbers observed in the albino retina. These results implicate Wnt signaling from the RPE to neural retina as a potential factor in the regulation of ipsilateral RGC production, and thus the albino phenotype.

KEYWORDS:

Ciliary margin zone; Retinal pigment epithelium; Wnt2b; Zic2

PMID:
30254141
PMCID:
PMC6240318
[Available on 2019-11-01]
DOI:
10.1242/dev.163212

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