期刊
CELLULAR AND MOLECULAR LIFE SCIENCES
卷 75, 期 7, 页码 1179-1190出版社
SPRINGER BASEL AG
DOI: 10.1007/s00018-017-2701-z
关键词
Epidermis; Gene regulation; Ectodermal dysplasia; Epidermal cell identity; Epigenetics
资金
- Radboud University fellowship
- Brazilian Science without Borders program
- [NWO/ALW/MEERVOUD/836.12.010]
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.
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