Abstract
Retinoids function as important regulatory signaling molecules during development, acting in cellular growth and differentiation both during embryogenesis and in the adult animal. In 1953, Fell and Mellanby first found that excess vitamin A can induce transdifferentiation of chick embryonic epidermis to a mucous epithelium (Fell, H.B.; Mellanby, E. Metaplasia produced in cultures of chick ectoderm by high vitamin A. J. Physiol. 1953, 119, 470–488). However, the molecular mechanism of this transdifferentiation process was unknown for a long time. Recent studies demonstrated that Gbx1, a divergent homeobox gene, is one of the target genes of all-trans retinoic acid (ATRA) for this transdifferentiation. Furthermore, it was found that ATRA can induce the epidermal transdifferentiation into a mucosal epithelium in mammalian embryonic skin, as well as in chick embryonic skin. In the mammalian embryonic skin, the co-expression of Tgm2 and Gbx1 in the epidermis and an increase in TGF-β2 expression elicited by ATRA in the dermis are required for the mucosal transdifferentiation, which occurs through epithelial-mesenchymal interaction. Not only does retinoic acid (RA) play an important role in mucosal transdifferentiation, periderm desquamation, and barrier formation in the developing mammalian skin, but it is also involved in hair follicle downgrowth and bending by its effect on the Wnt/β-catenin pathway and on members of the Runx, Fox, and Sox transcription factor families.
Highlights
Skin is composed of an epidermis, which is an epithelium derived from ectodermal tissue, and an underlying dermis, which is a connective tissue derived from mesenchyme of mesodermal origin.During the formation of skin and its appendages, e.g., feathers, scales, and hair, the epithelium, and mesenchyme are inducers and targets of each other [1]
Similar to the results obtained from keratinocyte cultures, retinol deficiency in the rat can cause squamous metaplasia and keratinization in a wide variety of nonkeratinized and secretory epithelia [9,10]; and excess retinol can induce epidermal mucous metaplasia in skin cultured from chick embryos [11]
Many of the abnormalities in pattern formation and organ formation that result from the addition of exogenous Retinoic acids (RAs) during embryogenesis are related in part to the ability of retinoids to change the pattern of expression of the clusters of homeobox genes in the embryo [14,15,16,17]
Summary
Skin is composed of an epidermis, which is an epithelium derived from ectodermal tissue, and an underlying dermis, which is a connective tissue derived from mesenchyme of mesodermal origin. During the formation of skin and its appendages, e.g., feathers, scales, and hair, the epithelium, and mesenchyme are inducers and targets of each other [1]. Similar to the results obtained from keratinocyte cultures, retinol deficiency in the rat can cause squamous metaplasia and keratinization in a wide variety of nonkeratinized and secretory epithelia [9,10]; and excess retinol can induce epidermal mucous metaplasia in skin cultured from chick embryos [11]. Many homeobox genes have been shown to change their expression in the skin as a response to RA [18,19,20]. It was demonstrated over a decade ago that Gbx. This review highlights our current understanding of the role of retinoic acid in the epidermal transdifferentiation of skin and its appendages
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