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. 2021 May 9;28:36. doi: 10.1186/s12929-021-00732-8

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© The Author(s) 2021

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 2 — Skin architecture and Notch pathway member distribution. (Left panel) Organization of human skin. The epidermis is the thinnest and most superficial layer of the skin, it is connected to the underlying dermis through the cutaneous basement membrane zone (BMZ), the highly specialized structure which connects the epidermis to the dermis ensuring skin integrity and stability against mechanical insults. Epidermis is arranged into four distinct layers: basal, spinous, granular and stratum corneum (or horny layer). The deepest layer of the epidermis, overlaying the BMZ, is the basal layer which is followed by the spinous and the granular layers whilst the stratum corneum is the outermost. Each layer is typified by keratinocytes (KCs) at various stages of differentiation. KCs of the basal layer are characterized by their ability to proliferate. Indeed, in the basal layer, epidermal stem cells (SCs) divide to self-renew and produce transient amplifying cells (also known as committed progenitors—CPs), which possess a more limited proliferation capability. In the early phases of differentiation, CPs detach from the BMZ and move toward the stratum corneum becoming terminally differentiated cells (TDs) devoid of nuclei. (Right panel) Expression pattern of Notch receptors (NOTCH1-4) and Notch ligands (JAG1 and DLL1) in human skin [143, 144]