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Differentiation. 2016 Dec;92(5):326-335. doi: 10.1016/j.diff.2016.05.001. Epub 2016 May 26.

Retinoic acid signalling in the development of the epidermis, the limbs and the secondary palate.

Author information

1
Department of Orthodontics and Craniofacial Biology, Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
2
Department of Molecular Developmental Biology, Radboud Institute for Molecular Life Sciences (RIMLS), P.O. Box 9101, 6500 HB Nijmegen, The Netherlands; Department of Human Genetics, Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
3
Department of Orthodontics and Craniofacial Biology, Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands; Department of Human Genetics, Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands; Department of Oral Health Sciences, KU Leuven, 3000 Leuven, Belgium.
4
Department of Orthodontics and Craniofacial Biology, Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. Electronic address: hans.vondenhoff@radboudumc.nl.

Abstract

Retinoic acid (RA), the active derivative of vitamin A, is one of the major regulators of embryonic development, including the development of the epidermis, the limbs and the secondary palate. In the embryo, RA levels are tightly regulated by the activity of RA synthesizing and degrading enzymes. Aberrant RA levels due to genetic variations in RA metabolism pathways contribute to congenital malformations in these structures. In vitro and in vivo studies provide considerable evidence on the effects of RA and its possible role in the development of the epidermis, the limbs and the secondary palate. In conjunction with other regulatory factors, RA seems to stimulate the development of the epidermis by inducing proliferation and differentiation of ectodermal cells into epidermal cells. In the limbs, the exact timing of RA location and level is crucial to initiate limb bud formation and to allow chondrogenesis and subsequent osteogenesis. In the secondary palate, the correct RA concentration is a key factor for mesenchymal cell proliferation during palatal shelf outgrowth, elevation and adhesion, and finally to allow bone formation in the hard palate. These findings are highly relevant to understanding the mechanism of RA signalling in development and in the aetiology of specific congenital diseases.

KEYWORDS:

Embryonic development; Epidermis; Limb; Palatogenesis; Retinoic acid; Secondary palate; Vitamin A

PMID:
27238416
DOI:
10.1016/j.diff.2016.05.001
[Indexed for MEDLINE]

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