PUBLICATION
Differences in neural crest sensitivity to ethanol account for the infrequency of anterior segment defects in the eye compared with craniofacial anomalies in a zebrafish model of fetal alcohol syndrome
- Authors
- Eason, J., Williams, A.L., Chawla, B., Apsey, C., Bohnsack, B.L.
- ID
- ZDB-PUB-170707-3
- Date
- 2017
- Source
- Birth defects research 109(15): 1212-1227 (Journal)
- Registered Authors
- Bohnsack, Brenda, Eason, Jessica, Williams, Antionette
- Keywords
- anterior segment, congenital eye disease, ethanol, eye development, fetal alcohol syndrome, neural crest, superoxide dismutase
- MeSH Terms
-
- Animals
- Apoptosis/drug effects
- Craniofacial Abnormalities/chemically induced
- Craniofacial Abnormalities/metabolism
- Disease Models, Animal
- Ethanol/adverse effects
- Eye/embryology
- Eye Abnormalities/chemically induced
- Eye Abnormalities/metabolism
- Female
- Fetal Alcohol Spectrum Disorders/metabolism*
- Fetal Alcohol Spectrum Disorders/physiopathology*
- Forkhead Transcription Factors
- Gene Expression Regulation, Developmental/drug effects
- In Situ Hybridization
- In Situ Nick-End Labeling/methods
- Mesoderm/metabolism
- Neural Crest/drug effects*
- Neural Crest/metabolism
- Neurogenesis/drug effects
- Pregnancy
- Reactive Oxygen Species/metabolism
- Transcription Factors/genetics
- Zebrafish/embryology
- Zebrafish/metabolism
- PubMed
- 28681995 Full text @ Birth Defects Res
Citation
Eason, J., Williams, A.L., Chawla, B., Apsey, C., Bohnsack, B.L. (2017) Differences in neural crest sensitivity to ethanol account for the infrequency of anterior segment defects in the eye compared with craniofacial anomalies in a zebrafish model of fetal alcohol syndrome. Birth defects research. 109(15):1212-1227.
Abstract
Background Ethanol (ETOH) exposure during pregnancy is associated with craniofacial and neurologic abnormalities, but infrequently disrupts the anterior segment of the eye. In these studies, we used zebrafish to investigate differences in the teratogenic effect of ETOH on craniofacial, periocular, and ocular neural crest.
Methods Zebrafish eye and neural crest development was analyzed by means of live imaging, TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assay, immunostaining, detection of reactive oxygen species, and in situ hybridization.
Results Our studies demonstrated that foxd3-positive neural crest cells in the periocular mesenchyme and developing eye were less sensitive to ETOH than sox10-positive craniofacial neural crest cells that form the pharyngeal arches and jaw. ETOH increased apoptosis in the retina, but did not affect survival of periocular and ocular neural crest cells. ETOH also did not increase reactive oxygen species within the eye. In contrast, ETOH increased ventral neural crest apoptosis and reactive oxygen species production in the facial mesenchyme. In the eye and craniofacial region, sod2 showed high levels of expression in the anterior segment and in the setting of Sod2 knockdown, low levels of ETOH decreased migration of foxd3-positive neural crest cells into the developing eye. However, ETOH had minimal effect on the periocular and ocular expression of transcription factors (pitx2 and foxc1) that regulate anterior segment development.
Conclusion Neural crest cells contributing to the anterior segment of the eye exhibit increased ability to withstand ETOH-induced oxidative stress and apoptosis. These studies explain the rarity of anterior segment dysgenesis despite the frequent craniofacial abnormalities in fetal alcohol syndrome. Birth Defects Research, 2017. © 2017 Wiley Periodicals, Inc.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping