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

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 via live imaging, TUNEL 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. Conclusions 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.

Vitamin E is necessary for zebrafish nervous system development

“…NC migration and differentiation is highly dependent on nutrient status 36,37 . Both pax2a and sox10 expression patterns are irregular in oxidative stress models [38][39][40] and errors in neurogenesis are marked by transcriptional changes of the Pax [41][42][43] and SoxE family of genes [43][44][45][46] .…”

Anti-Developmental Effects of Imazosulfuron on Zebrafish Embryos During Development

“…The eyes and brain contain diverse types of glial cells, including optic nerve, retina, neural crest cells, neurons, and astrocytes (Eason et al, 2017). Synthesized organotin compounds induced pyknosis and visual problems with normal retina apoptosis in zebrafish (Biehlmaier et al, 2001).…”

What's retinoic acid got to do with it? Retinoic acid regulation of the neural crest in craniofacial and ocular development

“…However, in the chick, there are two waves of migrating cells, and in zebrafish and mice, there is one continuous influx of neural crest cells into the developing eye. Despite these species differences, the general sequence of anterior segment formation remains consistent (Eason et al, 2017;Gage, Rhoades, Prucka, & Hjalt, 2005;Hay, 1979;Hay & Revel, 1969;Pei & Rhodin, 1970).…”

“…These neural crest cells coalesce around the lens and give rise to the corneal stroma, the iris stroma, and the aqueous outflow channels (Eason, Williams, Chawla, Apsey, & Bohnsack, 2017). In zebrafish, neural crest cells migrate in two pathways: (a) between the optic cup and surface ectoderm and (b) through the ocular fissure.…”

“…In zebrafish, neural crest cells migrate in two pathways: (a) between the optic cup and surface ectoderm and (b) through the ocular fissure. These neural crest cells coalesce around the lens and give rise to the corneal stroma, the iris stroma, and the aqueous outflow channels (Eason, Williams, Chawla, Apsey, & Bohnsack, 2017). In humans there are three separate migratory waves of neural crest cells that sequentially contribute first to the cornea, then to the iris, and finally to the aqueous outflow tract.…”