Retinoic acid-induced epidermal transdifferentiation in skin

Yoshihiro Akimoto, Mary Miyaji, Riyo Morimoto-Kamata, Yasuhiro Kosaka, Akiko Obinata

Research output: Contribution to journalReview article

1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)158-173
Number of pages16
JournalJournal of Developmental Biology
Volume2
Issue number3
DOIs
Publication statusPublished - Sep 1 2014

Keywords

  • All-trans retinoic acid (ATRA)
  • Epithelial-mesenchymal interaction
  • Feather-bud formation
  • Homeobox gene
  • Mucosal epithelium
  • Skin
  • Transdifferentiation

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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