Ethanol-induced neural crest apoptosis is coincident with their endogenous death, but is mechanistically distinct.
The ability of both acute and chronic ethanol exposures to elicit cell death within specific embryonic and adult tissues is believed to partly underlie ethanol's pathogenicity; however, the mechanism underlying this cell death is unknown. This study partially characterized the mechanism of ethanol-induced neural crest cell death in a chick embryo model of fetal alcohol syndrome. In situ DNA end-labeling demonstrated this cell death was apoptotic and occurred at embryonic ethanol levels as low as 42 mM. Regardless of the initial exposure time, this apoptosis always appeared at a distinct developmental time point simultaneous with the normal deletion of a cranial neural crest subset. This suggested that ethanol might act through aberrant activation of the endogenous death pathway; however, ethanol exposure failed to induce two components of this pathway, the homeotic transcription factor msx-2 and the growth factor bone morphogenetic protein 4. Both endogenous and ethanol-induced death were blocked by local application of an interleukin-1beta converting enzyme/CED-3 protease (caspase) inhibitor, showing that the two paths converge mechanistically and suggesting the potential to prevent this aspect of ethanol's teratogenicity. Ethanol exposure did not significantly alter cell proliferation within neural crest-populated regions, suggesting that susceptibility to ethanol-induced death did not involve exit from the cell cycle. Apoptotic deletion of cranial neural crest could partially explain the craniofacial deficits characteristic of the fetal alcohol syndrome.
Cartwright
M M
MM
Department of Nutritional Sciences, University of Wisconsin-Madison, 53706, USA.
Tessmer
L L
LL
Smith
S M
SM
D000328:Adult; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects*; D002642:Chick Embryo; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000473:pathology; D006801:Humans; D007231:Infant, Newborn; D009432:Neural Crest / Q000187:drug effects*; D011247:Pregnancy
D000431:Ethanol