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Review
. 2024 Jul 30;46(8):8239-8267.
doi: 10.3390/cimb46080487.

Skin Development and Disease: A Molecular Perspective

Iasonas Dermitzakis  1 , Despoina Chatzi  1 , Stella Aikaterini Kyriakoudi  1 , Nikolaos Evangelidis  1 , Efstratios Vakirlis  2 , Soultana Meditskou  1 , Paschalis Theotokis  1 , Maria Eleni Manthou  1
Affiliations
Review

Skin Development and Disease: A Molecular Perspective

Iasonas Dermitzakis et al. Curr Issues Mol Biol. .

Abstract

Skin, the largest organ in the human body, is a crucial protective barrier that plays essential roles in thermoregulation, sensation, and immune defence. This complex organ undergoes intricate processes of development. Skin development initiates during the embryonic stage, orchestrated by molecular cues that control epidermal specification, commitment, stratification, terminal differentiation, and appendage growth. Key signalling pathways are integral in coordinating the development of the epidermis, hair follicles, and sweat glands. The complex interplay among these pathways is vital for the appropriate formation and functionality of the skin. Disruptions in multiple molecular pathways can give rise to a spectrum of skin diseases, from congenital skin disorders to cancers. By delving into the molecular mechanisms implicated in developmental processes, as well as in the pathogenesis of diseases, this narrative review aims to present a comprehensive understanding of these aspects. Such knowledge paves the way for developing innovative targeted therapies and personalised treatment approaches for various skin conditions.

Keywords: appendages; cancer; development; disease; embryogenesis; epidermis; hair follicle; molecular cues; skin; sweat glands.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Molecular cues orchestrating epidermal specification, commitment, stratification, and terminal differentiation. AP-2γ: Activating protein 2γ. BMP: Bone morphogenetic protein. Ca2+: Calcium ion. CDH1: Cadherin 1. FGF: Fibroblast growth factor. GRHL3: Grainyhead-like transcription factor 3. HES1: Hes family bHLH transcription factor 1. IRF6: Interferon regulatory factor 6. Notch: Neurogenic locus Notch homolog protein. OVOL1: Ovo-like transcriptional repressor 1. Perp: P53 apoptosis effector related to PMP22. PKC: Protein kinase C. RBPJ: Recombination signal-binding protein for immunoglobulin kappa J region. SFN: Stratifin. ZNF750: Zinc finger protein 750. Created with BioRender.com.
Figure 2
Figure 2
Molecular drivers regulating hair follicle fate specification and the initiation of its growth. Green-coloured cues represent the positive regulators, while red-coloured cues refer to the negative ones. BMPs: Bone morphogenetic proteins. Dkks: Dickkopf WNT signalling pathway inhibitors. Eda-A1: Ectodysplasin-A1. EdaR: Ectodysplasin A receptor. FGF20: Fibroblast growth factor 20. LEF1: Lymphoid enhancer binding factor 1. NF-κB: Nuclear factor kappa B. PDGFA: Platelet-derived growth factor A. SHH: Sonic Hedgehog. TGFβ2: Transforming growth factor beta 2. Created with BioRender.com.
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