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Cell Mol Life Sci. 2018 Apr;75(7):1179-1190. doi: 10.1007/s00018-017-2701-z. Epub 2017 Nov 4.

Master regulatory role of p63 in epidermal development and disease.

Author information

1
Department of Molecular Developmental Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Radboud University, 274, Postbus 9101, 6500HB, Nijmegen, The Netherlands.
2
CAPES Foundation, Ministry of Education of Brazil, Brasília, Brazil.
3
Department of Molecular Developmental Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Radboud University, 274, Postbus 9101, 6500HB, Nijmegen, The Netherlands. jo.zhou@radboudumc.nl.
4
Department of Human Genetics, Radboud University Medical Center, 855, Postbus 9101, 6500HB, Nijmegen, The Netherlands. jo.zhou@radboudumc.nl.

Abstract

The transcription factor p63 is a master regulator of epidermal development. Mutations in p63 give rise to human developmental diseases that often manifest epidermal defects. In this review, we summarize major p63 isoforms identified so far and p63 mutation-associated human diseases that show epidermal defects. We discuss key roles of p63 in epidermal keratinocyte proliferation and differentiation, emphasizing its master regulatory control of the gene expression pattern and epigenetic landscape that define epidermal fate. We subsequently review the essential function of p63 during epidermal commitment and transdifferentiation towards epithelial lineages, highlighting the notion that p63 is the guardian of the epithelial lineage. Finally, we discuss current therapeutic development strategies for p63 mutation-associated diseases. Our review proposes future directions for dissecting p63-controlled mechanisms in normal and diseased epidermal development and for developing therapeutic options.

KEYWORDS:

Ectodermal dysplasia; Epidermal cell identity; Epidermis; Epigenetics; Gene regulation

PMID:
29103147
PMCID:
PMC5843667
DOI:
10.1007/s00018-017-2701-z
[Indexed for MEDLINE]
Free PMC Article

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