Retinoic Acid-Induced Epidermal Transdifferentiation in Skin

Journal of Developmental Biology

Yoshihiro Akimoto¹  Mary Miyaji²  Riyo Morimoto-Kamata²  Yasuhiro Kosaka² 

[1] Department of Anatomy, Kyorin University School of Medicine, Mitaka, Tokyo 181-8611, Japan;Department of Physiological Chemistry II, Faculty of Pharmaceutical Sciences, Teikyo University, Sagamihara, Kanagawa 252-5195, Japan; E-Mails:

关键词: all-trans retinoic acid (ATRA);    skin;    homeobox gene;    feather-bud formation;    transdifferentiation;    mucosal epithelium;    epithelial-mesenchymal interaction;   

DOI  :  10.3390/jdb2030158

来源: mdpi

【 摘 要 】

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.

【 授权许可】

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© 2014 by the authors; licensee MDPI, Basel, Switzerland.