Abstract
Intensive research effort has focused on cellular and molecular mechanisms that regulate skin biology, including the phenomenon of scar-free skin healing during foetal life. Transcription factors are the key molecules that tune gene expression and either promote or suppress gene transcription. The epidermis is the source of transcription factors that regulate many functions of epidermal cells such as proliferation, differentiation, apoptosis, and migration. Furthermore, the activation of epidermal transcription factors also causes changes in the dermal compartment of the skin. This review focuses on the transcription factor Foxn1 and its role in skin biology. The regulatory function of Foxn1 in the skin relates to physiological (development and homeostasis) and pathological (skin wound healing) conditions. In particular, the pivotal role of Foxn1 in skin development and the acquisition of the adult skin phenotype, which coincides with losing the ability of scar-free healing, is discussed. Thus, genetic manipulations with Foxn1 expression, specifically those introducing conditional Foxn1 silencing in a Foxn1+/+ organism or its knock-in in a Foxn1−/− model, may provide future perspectives for regenerative medicine.
Highlights
Skin, the largest organ in the body, acts as the outermost barrier to protect against water loss and a variety of external insults [1,2]
We summarised the findings that have considerably advanced the understanding of the role of Foxn1 in the skin as it has been investigated in various settings, including skin morphogenesis, homeostasis and wound healing (Table 2)
Does Foxn1 priming develop during neonatal life and lead the skin to acquire characteristic cellular features of skin maturity (Scheme 2)? Our recent sequencing data show [41] that the employed skin and epidermis from mouse embryos (E14, model of skin regeneration; E18, model of skin repair) and their adult counterparts, represented by nude and C57BL/6J wild-type animals, demonstrated that Foxn1 acts as the transcriptomic signature that determines skin fate
Summary
The largest organ in the body, acts as the outermost barrier to protect against water loss and a variety of external insults [1,2]. We focus on the transcription factor Foxn, whose expression is restricted to organs with multilayered epithelia structures: the thymus [11,12] and skin [13,14,15,16]. It was shown that an inactivating mutation in the Foxn gene causes the nude phenotype, which is characterised by a lack of visible hair, abnormal development of the epidermis and a severe immunodeficiency due to thymus dysgenesis [22,25]. We review the current knowledge of Foxn, focusing on its expression and role in the skin during development, homeostasis and wound repair
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