Induction of Mucous Metaplasia in Chick Embryonic Skin by Retinol‐Pretreated Embryonic Chick or Quail Dermal Fibroblasts through Cell‐Cell Interaction: Correlation of a Transient Increase in Retinoic Acid Receptor β mRNA in Retinol‐Treated Dermal Fibroblasts with Their Competence to Induce Epidermal Mucous Metaplasia

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Abstract
Epidermal mucous metaplasia of 13‐day‐old chick embryonic tarsometatarsal skin can be induced by culture in medium containing 20 μM retinol for only 8 hr and then in a chemically defined medium without retinol for 2 days. Retinol primarily affects the dermal cells, which then transform the epithelial cells into mucus‐secreting cells. In this study, we developed a system using a combination of retinol‐pretreated chick or quail dermal fibroblasts and chick skin, and showed that retinol‐pretreated quail embryonic dermal fibroblasts invaded the dermis of chick embryonic skin to beneath the epidermal basal cells within 1 day of culture and induced metaplasia, suggesting that epidermal mucous metaplasia of the skin was induced by the direct interaction of retinol‐pretreated dermal fibroblasts with the epidermal cells or by low diffusible paracrine factor produced by the fibroblasts. Increase in retinoic acid receptor β (RARβ) mRNA in dermal fibroblasts was observed after 8 hr‐treatment with retinol which preceded morphological changes induced by retinol and this increase was correlated with the competence of the dermal fibroblasts to induce epidermal mucous metaplasia. Thus some gene product(s) controlled by RARβ in dermal fibroblasts may be an essential signal for induction of epidermal mucous metaplasia.