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J. Dev. Biol. 2014, 2(3), 158-173; doi:10.3390/jdb2030158

Retinoic Acid-Induced Epidermal Transdifferentiation in Skin

1,* , 2,†
2,‡, 2,§
1 Department of Anatomy, Kyorin University School of Medicine, Mitaka, Tokyo 181-8611, Japan 2 Department of Physiological Chemistry II, Faculty of Pharmaceutical Sciences, Teikyo University, Sagamihara, Kanagawa 252-5195, Japan Present address: Departments of Neurogenomics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Shikata-cho, Okayama 700-8558, Japan. Present address: Faculty of Pharma Science, Laboratory of Host Defence, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan. § Present address: Departments of Pediatrics, The University of Utah School of Medicine, Eccles Institute of Human Genetics, 15 North 2030 East, Salt Lake City, UT 84112, USA.
* Author to whom correspondence should be addressed.
Received: 12 March 2014 / Revised: 4 June 2014 / Accepted: 9 June 2014 / Published: 26 June 2014
(This article belongs to the Special Issue Retinoids in Development)
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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.
Keywords: all-trans retinoic acid (ATRA); skin; homeobox gene; feather-bud formation; transdifferentiation; mucosal epithelium; epithelial-mesenchymal interaction all-trans retinoic acid (ATRA); skin; homeobox gene; feather-bud formation; transdifferentiation; mucosal epithelium; epithelial-mesenchymal interaction
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Akimoto, Y.; Miyaji, M.; Morimoto-Kamata, R.; Kosaka, Y.; Obinata, A. Retinoic Acid-Induced Epidermal Transdifferentiation in Skin. J. Dev. Biol. 2014, 2, 158-173.

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