title: Nuanced but significant: how ethanol perturbs avian cranial neural crest cell actin cytoskeleton, migration and proliferation.
abstract: Children with fetal alcohol syndrome (FAS) display striking craniofacial abnormalities. These features are proposed to result from perturbations in the morphology and function of cranial neural crest cells (cNCCs), which contribute significantly to the craniofacial complex. While certain pathways by which this may occur have been suggested, precise teratogenic mechanisms remain intensely investigated, as does the question of the teratogenic dose. The present study focused on examining how avian cNCC actin cytoskeleton, migratory distance, and proliferation are affected ex vivo by exposure to ethanol concentrations that simulate maternal intoxication. Chick cNCCs were cultured in 0.2% and 0.4% v/v ethanol. Distances migrated by both ethanol-treated and control cells at 24 and 48 h were recorded. Following phalloidin immunocytochemistry, treated and control cNCCs were compared morphologically and quantitatively. Apoptosis and proliferation in control versus treated cNCCs were also studied. Chick cNCCs cultured in ethanol lost their spindle-like shapes and their ordered cytoskeleton. There was a significant stage-dependent effect on cNCC migration at 24 h (p = 0.035), which was greatest at stage 10 (HH). Ethanol treatment for 48 h revealed a significant main effect for ethanol, chiefly at the 0.4% level. There was also an interaction effect between ethanol dose and stage of development (stage 9 HH). Actin microfilament disruption was quantitatively increased by ethanol at the doses studied while cNCC proliferation was increased but not significantly. Ethanol had no effect on cNCC apoptosis. At ethanol levels likely to induce human FAS, avian cNCCs exhibit various subtle, potentially significant changes in morphology, migration, and proliferation, with possible consequences for fated structures.
authors.affiliation: School of Anatomical Sciences, Faculty of Health Sciences, University of the Witwatersrand Johannesburg, 7 York Road, Parktown 2193, South Africa. olusegun.oyedele@ubc.ca
authors.forename: Olusegun O
authors.initials: OO
authors.lastname: Oyedele
authors.forename: Beverley
authors.initials: B
authors.lastname: Kramer
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects* / Q000648:ultrastructure; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002642:Chick Embryo; D000431:Ethanol / Q000009:adverse effects*; D009432:Neural Crest / Q000166:cytology* / Q000187:drug effects* / Q000196:embryology; D013723:Teratogens / Q000494:pharmacology
chemical_list: D013723:Teratogens; D000431:Ethanol