Effect of retinoids on the differentiation of chick embryo metatarsal skin explants

Twelve retinoids were evaluated in organ culture for activity in modulating epithelial differentiation of metatarsal skin explants from 13-day chick embryos. The epithelium differentiated into a squamous, keratinizing epidermis; but, in the presence of active retinoids, keratinization was inhibited, and a mucous metaplasia developed. The methyl-keto and 1-methoxyethyl cyclopentenyl analogs of retinoic acid were about tenfold more effective than retinoic acid in altering epithelial differentiation. The dichlorophenyl analog exhibited about the same activity as retinoic acid. The following analogs were one-half to one-third as effective as retinoic acid in inhibiting keratinization: the chlorotrimethylphenyl analog of retinoic acid and the 13-cis, 10-fluoro analog of trimethylmethoxyphenyl methyl retinoate. The other 7 retinoids were essentially not active at the concentration tested (1.4--2.0 x 10(-5) M). The activity of synthetic retinoids in altering epithelial differentiation may be related to their ability to affect or treat epithelial lesions provided that modification of the retinoid molecule can enhance its activity and decrease toxicity.