Notch signaling: Its role in epidermal homeostasis and in the pathogenesis of skin diseases

Summary Skin undergoes self-renewal throughout life. Terminally differentiated keratinocytes, namely the corneocytes, are continually shed from the surface of the skin, whereas immature cells produce progeny that proceed through the differentiation process. Notch signaling controls a number of cellu...

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Bibliographic Details
Published in:Journal of dermatological science 2008-03, Vol.49 (3), p.187-194
Main Authors: Okuyama, Ryuhei, Tagami, Hachiro, Aiba, Setsuya
Format: Article
Language:English
Subjects:
Animals
Cell Differentiation
Cell Proliferation
Cross-talk
Dermatology
Differentiation
Homeostasis
Humans
Keratinocyte
Langerhans Cells - physiology
Melanocytes - physiology
Notch
Oncogenesis
Psoriasis
Receptors, Notch - physiology
Signal Transduction - physiology
Skin - cytology
Skin Diseases - etiology
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Summary:Summary Skin undergoes self-renewal throughout life. Terminally differentiated keratinocytes, namely the corneocytes, are continually shed from the surface of the skin, whereas immature cells produce progeny that proceed through the differentiation process. Notch signaling controls a number of cellular processes including cell fate decision, proliferation, differentiation and survival/apoptosis. Hence, Notch and its ligands are expressed in multiple tissues including the skin, where they are abundantly expressed in the epidermis. Notch activation results in the promotion of growth arrest and the onset of differentiation, therefore suggesting that specific Notch activation may regulate skin homeostasis by balancing these processes, i.e. Notch signaling functions as a molecular switch that controls the transition of cells between skin layers during the epidermal differentiation process. Recent advances in the study of Notch signaling have confirmed that there is cross-talk between the Notch signaling pathway and a variety of other signaling molecules including Sonic hedgehog (Shh), β-catenin and the p53 family member, p63. The absence of Notch activity allows Wnt and Shh signaling to persist in a tissue where they are normally repressed. In addition, Notch counteracts the action of p63 to maintain immature cell characteristics. However, aberrant Notch signaling results in the development of psoriasis and skin cancers such as squamous cell carcinoma, basal cell carcinoma and malignant melanoma. Future efforts to further define how Notch controls cell proliferation and differentiation may lead to the application of Notch in new therapies for various skin diseases.
ISSN:0923-1811
1873-569X
DOI:10.1016/j.jdermsci.2007.05.017