Patterned acquisition of skin barrier function during development
Abstract
Skin barrier function is conferred by the outer layer of epidermis, the stratum corneum, and is essential for terrestrial life. Quantitative trans-epidermal water loss assays show that barrier forms late in embryogenesis, permitting the foetus to survive a terrestrial environment at birth. Using qualitative in situ assays for skin permeability, we show that barrier forms in a patterned manner late in mouse gestation. Barrier forms at specific epidermal sites, then spreads around the embryo as a moving front. The moving front of permeability change is accompanied by multiple changes in the outer, stratum corneum-precursor cells. We use the permeability assays to show that final stages of cornified envelope assembly are coordinated with initial stages of barrier formation. Hence the whole-mount permeability assays record developmental acquisition of a known, essential component of the adult barrier. We demonstrate the authenticity of the whole-mount assays after maternal glucocorticoid therapy (known to accelerate barrier formation) and in additional species including the rat where barrier formation is well characterized by TEWL assay (Aszterbaum, M., Menon, G. K., Feingold, K. R. and Williams, M. L. Pediatr. Res. 31, 308-317). The demonstration of patterned barrier formation in other species suggests patterned change as the universal mode of embryonic barrier acquisition. These results highlight the importance of patterning as a mode of epidermal maturation during development.
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A functional SC barrier is first formed in dorsal epidermis at embryonic day (E)16.5, spreading only to the ventral side one day later.
“A functional SC barrier is first formed in dorsal epidermis at embryonic day (E)16.5, spreading only to the ventral side one day later10, 20.”
From E-cadherin integrates mechanotransduction and EGFR signaling to control junctional tissue polarization and tight junction positioning (2017) · cites this paper as [20]
EGFR recruitment to suprabasal junctions at E16.5 coincides with ZO-1 and vinculin recruitment to the most viable suprabasal layer and with initiation of barrier function.
“This coincided with ZO-1 and vinculin recruitment to the most viable suprabasal layer (Fig. 4a, b) and with initiation of barrier function20.”
From E-cadherin integrates mechanotransduction and EGFR signaling to control junctional tissue polarization and tight junction positioning (2017) · cites this paper as [20]
In our K14-cre/Ecad Fl/À mice, E-cadherin is already almost completely absent at E15.5 shortly before the onset of barrier formation, perhaps explaining why loss of E-cadherin has more dramatic consequences in our mice.
“In our K14-cre/Ecad Fl/À mice, E-cadherin is already almost completely absent at E15.5 (Figure 1C) shortly before the onset of barrier formation (Hardman et al, 1998), perhaps explaining why loss of E-cadherin has more dramatic consequences in our mice.”
From E‐cadherin is essential for in vivo epidermal barrier function by regulating tight junctions (2005) · cites this paper as Hardman et al, 1998
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- Authors
- Hardman, M. J., Sisi, P., Banbury, D. N., & Byrne, C.
- Affiliations
- University of Manchester (GB)
- Corresponding author
- Byrne, Carolyn
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 1998-04-15
- Volume
- 125
- Issue
- 8
- Pages
- 1541-1552
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- OpenAlex
- W2097754683
- Cited by
- 385
- References
- 1
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 7 · 2023: 4 · 2022: 9 · 2021: 9 · 2020: 7 · 2019: 10 · 2018: 15 · 2017: 17 · 2016: 15 · 2015: 15 · 2014: 20 · 2013: 13 · 2012: 17
- FWCI
- 3.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Development (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Wellcome Trust
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advancements in Transdermal Drug Delivery
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Keywords
- skin barrier function, stratum corneum, embryonic development, transepidermal water loss, skin permeability, epidermal maturation, rats
- MeSH terms
- Epidermal Cells, Filaggrin Proteins, Animals, Betamethasone, Epidermis, Female, Embryonic and Fetal Development, Gestational Age, Intermediate Filament Proteins, Maternal-Fetal Exchange, Mice, Inbred ICR, Permeability, Pregnancy, Skin, Skin Physiological Phenomena, Species Specificity, Body Patterning, Mice, Rats
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