Isotretinoin alters morphology, polarity, and motility of neural crest cells in culture.

Migrating neural crest cells (NCCs) contribute to a diverse array of vertebrate head and neck structures. Retinoids are proven human and animal teratogens. To elucidate isotretinoin's effects, cranial and trunk neural folds were microdissected from chick embryos and cultured. Image analysis and immunostaining were used to quantitate cell behavior. We found that a higher proportion of Stage 8, 9, and 10 treated NCCs were rounded and clustered. Medians and means for cell area, perimeter, and elongation index were lower for treated cells from Stage 9 and 10 embryos, but not from Stage 8. Cumulative medians and means for changes in area and perimeter, and cell migration were similarly lower. Thus interference with the transitory basal activity of the cytoskeleton that adjusts and determines cell-substratum adhesion, spreading, elongation, and migration may be the mechanism by which isotretinoin acts on NCCs in slightly older embryos.