PUBLICATION
Retinal Wnt signaling defect in a zebrafish fetal alcohol spectrum disorder model
- Authors
- Muralidharan, P., Sarmah, S., Marrs, J.A.
- ID
- ZDB-PUB-180802-8
- Date
- 2018
- Source
- PLoS One 13: e0201659 (Journal)
- Registered Authors
- Marrs, James A., Sarmah, Swapnalee
- Keywords
- none
- MeSH Terms
-
- Disease Models, Animal
- Zebrafish/embryology
- Zebrafish/genetics
- Retina/drug effects
- Retina/metabolism
- Retina/pathology*
- Nerve Tissue Proteins/genetics
- Basic Helix-Loop-Helix Transcription Factors/genetics
- Fetal Alcohol Spectrum Disorders/metabolism*
- Fetal Alcohol Spectrum Disorders/pathology
- Folic Acid/pharmacology
- Cell Proliferation/drug effects
- Animals
- Tretinoin/pharmacology
- Cell Differentiation
- Receptors, Notch/metabolism
- Pregnancy
- Photoreceptor Cells, Vertebrate/cytology
- Photoreceptor Cells, Vertebrate/drug effects
- Photoreceptor Cells, Vertebrate/metabolism
- Female
- Wnt Signaling Pathway
- Ethanol/adverse effects*
- Retinal Diseases/chemically induced
- Retinal Diseases/metabolism*
- Retinal Diseases/pathology
- Embryo, Nonmammalian/drug effects
- PubMed
- 30067812 Full text @ PLoS One
Citation
Muralidharan, P., Sarmah, S., Marrs, J.A. (2018) Retinal Wnt signaling defect in a zebrafish fetal alcohol spectrum disorder model. PLoS One. 13:e0201659.
Abstract
Fetal alcohol spectrum disorder caused by prenatal alcohol exposure includes ocular abnormalities (microphthalmia, photoreceptor dysfunction, cataracts). Zebrafish embryos exposed to ethanol from gastrulation through somitogenesis show severe ocular defects, including microphthalmia and photoreceptor differentiation defects. Ethanol-treated zebrafish had an enlarged ciliary marginal zone (CMZ) relative to the retina size and reduced Müller glial cells (MGCs). Ethanol exposure produced immature photoreceptors with increased proliferation, indicating cell cycle exit failure. Signaling mechanisms in the CMZ were affected by embryonic ethanol exposure, including Wnt signaling in the CMZ, Notch signaling and neurod gene expression. Retinoic acid or folic acid co-supplementation with ethanol rescued Wnt signaling and retinal differentiation. Activating Wnt signaling using GSK3 inhibitor (LSN 2105786; Eli Lilly and Co.) restored retinal cell differentiation pathways. Ethanol exposed embryos were treated with Wnt agonist, which rescued Wnt-active cells in the CMZ, Notch-active cells in the retina, proliferation, and photoreceptor terminal differentiation. Our results illustrate the critical role of Wnt signaling in ethanol-induced retinal defects.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping