Effects of retinoic acid on embryonic chick skin.

The influence of vitamin A on differentiating epithelia was examined in explants of skin from 14-day chick embryos exposed to retinoic acid (RA) in low, moderate, and high doses. The changes observed in RA-treated cultures are both dose- and time-dependent and are reversible when explants are transferred to control medium. The periderm sloughs prematurely and horizontal stratification is lost. Keratinization is inhibited and fewer desmosomes and tonofilaments are seen. Surface epidermal cells develop microvilli, bulge upwards, and detach. Golgi elements, rough endoplasmic reticulum, and polyribosomes are unusually prominent. Mucin granules form and gland-like structures develop with intercellular canaliculi characterized by tight junctions, brush borders, and dense secretory contents. On the basis of present evidence there are several possible mechanisms by which RA could alter epidermal differentiation. RA-induced gaps in the basal lamina allow direct contact between epidermal basal cells and fibroblasts and collagen fibers which could result in inappropriate dermal signals reaching the epidermis. In younger embryos the entire epidermis, including the mitotically inactive surface cells, appears to respond to RA, and this could imply an epigenetic modulation of cell phenotype. Finally, after the formation of a stratum corneum in older embryos only the relatively undifferentiated basal layer shows a metaplastic response, indicating that RA could be acting directly on the genome.