title: Increased cell death and reduced neural crest cell numbers in ethanol-exposed embryos: partial basis for the fetal alcohol syndrome phenotype.
abstract: Fetal alcohol syndrome (FAS) is characterized by growth retardation, craniofacial malformations, and heart and neural defects; the cellular and molecular mechanism(s) responsible for ethanol's teratogenicity remains unknown. Although the phenotype suggests that prenatal ethanol exposure perturbs neural crest cell development, direct proof that these cells are an in utero target is still lacking. Previous research suggested that cranial neural crest cells are eliminated by ethanol-induced apoptosis. We tested this hypothesis using a chick embryo model of FAS. A single dose of ethanol, chosen to achieve a concentration of 35-42 mg/dl, was injected in ovo at gastrulation and resulted in growth retardation, craniofacial foreshortening, and disrupted hindbrain segmentation. Ethanol exposure enhanced cell death within areas populated by cranial neural crest cells, particularly in the hindbrain and craniofacial mesenchyme. In contrast, control embryos had limited cell death within these regions. Subsequent immunolabeling with neural crest cell-specific antibody revealed that ethanol treatment resulted in fewer neural crest cell numbers, whereas neural crest migration patterns were unaffected by ethanol. These results suggest that prenatal ethanol exposure leads to loss of cranial neural crest cells. Such a loss could result, in part, in the phenotype characteristic of FAS.
authors.affiliation: Department of Nutritional Sciences, University of Wisconsin-Madison 53706, USA.
authors.forename: M M
authors.initials: MM
authors.lastname: Cartwright
authors.forename: S M
authors.initials: SM
authors.lastname: Smith
mesh_terms: D000818:Animals; D002452:Cell Count / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects*; D002642:Chick Embryo; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D063647:Fetal Alcohol Spectrum Disorders / Q000196:embryology* / Q000473:pathology; D009432:Neural Crest / Q000187:drug effects* / Q000196:embryology / Q000473:pathology