Abstract
We have described the clinical manifestations of isotretinoin (ISO) neuroembryopathy (J Ped, 105, 595, 1984) and with others have suggested that disturbances in neural crest development may underlie the pathogenesis of this teratogenic disorder (NEJM 313, 832, 1985). To investigate this possibility in a controlled experimental situation, cranial neural crest explant cultures were exposed to different concentrations of ISO (2 and 20 ug/ml medium) and cell morphology was monitored at 24 hour intervals for a total/ of 5 days using inverted phase contrast microscopy. In contrast to the control cultures of confluent flattened cells, ISO treated crest cells became rounded or spindle shaped, separated from their neighbors, and frequently detached from the substrate or clumped together. Similiar changes in morphology occurred in trunk neural crest cultures but not in neural tube cells or in cardiac fibroblasts. Exposure to ISO did not appear to change the amount or distribution of antibody binding to cell surface antigens HNK-1 or CSAT. Taken together, these results suggest that ISO selectively effects neural crest cells by decreasing their cell-substratum adhesion and strongly supports the hypothesis that ISO associated birth defects in humans may be caused by abnormalities in neural crest development.
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