This study was supported by Grant 940727 from the University of Wisconsin Graduate School. S.M.S. is the recipient of a Future Leaders in Nutrition Award from the International Life Sciences Institute.
Stage-Dependent Effects of Ethanol on Cranial Neural Crest Cell Development: Partial Basis for the Phenotypic Variations Observed in Fetal Alcohol Syndrome
Article first published online: 11 APR 2006
Alcoholism: Clinical and Experimental Research
Volume 19, Issue 6, pages 1454–1462, December 1995
How to Cite
Cartwright, M. M. and Smith, S. M. (1995), Stage-Dependent Effects of Ethanol on Cranial Neural Crest Cell Development: Partial Basis for the Phenotypic Variations Observed in Fetal Alcohol Syndrome. Alcoholism: Clinical and Experimental Research, 19: 1454–1462. doi: 10.1111/j.1530-0277.1995.tb01007.x
- Issue published online: 11 APR 2006
- Article first published online: 11 APR 2006
- Received for publication January 27, 1995; accepted June 30, 1995
- Fetal Alcohol Syndrome;
- Craniofacial Development;
- Neural Crest Cells;
- Programmed Cell Death
Fetal alcohol syndrome (FAS) is characterized by growth retardation, mental deficiencies, and numerous craniofacial and neuronal anomalies; the type and severity of these defects may be related to the time and dose of maternal ethanol exposure. Ethanol administered during presomitic stages results in the typical FAS craniofacial phenotype and is accompanied by a loss of cranial neural crest cells (CNCCs) through ethanol-induced cell death. However, the stage-specific effects of ethanol on the CNCC population is unknown. We examined the effects of ethanol on CNCC populations by treating in ovo chick embryos with a single ethanol dose (0.43 mmol/egg) at various stages of CNCC development, and corresponding to the first 3–4 weeks of human gestation. Ethanol treatment induced cell death and reduced CNCC populations in patterns consistent with observed dysmorphologies of CNCC-derived cranial structures. The precise population affected was dependent on the timing of ethanol exposure. Treatment at gastrulation or neurulation induced cell death and losses of CNCC populations, particularly those in rostral positions, and resulted in more severe craniofacial defects. In contrast, treatment at early somitic stages (4–16 somites) induced cell death, primarily within caudal CNCC populations, but resulted in less severe craniofacial defects, suggesting an increased capacity for recovery. These results suggest that there are distinct developmental windows during which the CNCCs may be particularly susceptible to ethanol-induced cell death. We conclude that ethanol exposure seems to affect specific events adversely during neural crest development. The timing of embryonic ethanol exposure relative to CNCC development could account, in part, for the heterogenous craniofacial defects observed in FAS.