Deconstructing the skin: cytoarchitectural determinants of epidermal morphogenesis

Simpson, Cory L.; Patel, Dipal; Green, Kathleen J.

doi:10.1038/nrm3175

Cited by 413 publications

(425 citation statements)

References 192 publications

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“…A similar elastic response was also found in particle-tracking microrheology experiments on epithelial cells (20). Furthermore, on the level of transgenic mice and patients with heritable fragility of the epidermis, a clear correlation between molecular integrity of keratin filaments (K5 and K14) and mechanical toughness of epithelia was shown (21,22).…”

supporting

confidence: 49%

Keratins as the main component for the mechanical integrity of keratinocytes

Ramms

Fabris

Windoffer

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

192

187

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Keratins are major components of the epithelial cytoskeleton and are believed to play a vital role for mechanical integrity at the cellular and tissue level. Keratinocytes as the main cell type of the epidermis express a differentiation-specific set of type I and type II keratins forming a stable network and are major contributors of keratinocyte mechanical properties. However, owing to compensatory keratin expression, the overall contribution of keratins to cell mechanics was difficult to examine in vivo on deletion of single keratin genes. To overcome this problem, we used keratinocytes lacking all keratins. The mechanical properties of these cells were analyzed by atomic force microscopy (AFM) and magnetic tweezers experiments. We found a strong and highly significant softening of keratin-deficient keratinocytes when analyzed by AFM on the cell body and above the nucleus. Magnetic tweezers experiments fully confirmed these results showing, in addition, high viscous contributions to magnetic bead displacement in keratin-lacking cells. Keratin loss neither affected actin or microtubule networks nor their overall protein concentration. Furthermore, depolymerization of actin preserves cell softening in the absence of keratin. On reexpression of the sole basal epidermal keratin pair K5/14, the keratin filament network was reestablished, and mechanical properties were restored almost to WT levels in both experimental setups. The data presented here demonstrate the importance of keratin filaments for mechanical resilience of keratinocytes and indicate that expression of a single keratin pair is sufficient for almost complete reconstitution of their mechanical properties.

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supporting

confidence: 49%

Keratins as the main component for the mechanical integrity of keratinocytes

Ramms

Fabris

Windoffer

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

192

187

View full text Add to dashboard Cite

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“…In humans and the mouse, 28 type I keratins (KtyI) and 26 type II keratins (KtyII) genes are predominantly expressed as pair-specific combinations of types I and II keratin proteins, respectively, in epithelial cells and tissues. The major impact of keratins on cell integrity and adhesion is most obvious in the epidermis, in addition to embryonic epithelia (Simpson et al 2011;Bouameur and Magin 2017). The basal compartment expresses the keratin pair KRT5/KRT14, organized in loose bundles that extend from hemidesmosomes and desmosomes.…”

Section: Role Of Ifs In Mechanical Stability Composition Assembly Amentioning

confidence: 99%

“…Analogous to desmosomes, keratin concentration increases from 40 mg/ml in basal keratinocytes to probably twice as much in terminally differentiated keratinocytes (Sun and Green 1978;Feng et al 2013). The above keratin expression pattern varies, for example, during epidermal injury, which triggers the rapid induction of KRT6, -16, and -17 at the wound edge at the expense of KRT1/ 10, accompanied by fewer and less adhesive desmosomes (Garrod and Chidgey 2008;Simpson et al 2011). KRT6, KRT16, and KRT17 are also expressed in hair follicles and the nails (Moll et al 2008).…”

Section: Role Of Ifs In Mechanical Stability Composition Assembly Amentioning

confidence: 99%

Desmosomes and Intermediate Filaments: Their Consequences for Tissue Mechanics

Hatzfeld

Keil

Magin

2017

Cold Spring Harb Perspect Biol

114

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Adherens junctions (AJs) and desmosomes connect the actin and keratin filament networks of adjacent cells into a mechanical unit. Whereas AJs function in mechanosensing and in transducing mechanical forces between the plasma membrane and the actomyosin cytoskeleton, desmosomes and intermediate filaments (IFs) provide mechanical stability required to maintain tissue architecture and integrity when the tissues are exposed to mechanical stress. Desmosomes are essential for stable intercellular cohesion, whereas keratins determine cell mechanics but are not involved in generating tension. Here, we summarize the current knowledge of the role of IFs and desmosomes in tissue mechanics and discuss whether the desmosome-keratin scaffold might be actively involved in mechanosensing and in the conversion of chemical signals into mechanical strength.

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“…The final step of the differentiation process of epidermal cells is the formation of the cornified layer, which occurs in the mouse embryo between E17.5 -E18.5 (Byrne et al 2003). Cells of the granular epidermal layer undergo cornification, which represents a unique form of cell death and includes formation of the cytoplasmic cornified envelope, a submembranous structure, in which intermediate filaments, proteins, lipids, fragments of degraded organelles, and nuclear remnants are cross-linked (Simpson et al 2011).…”

Section: The P53 Family and Its Isoformsmentioning

confidence: 99%

p53/p63/p73 in the Epidermis in Health and Disease

Botchkarev

Flores

2014

Cold Spring Harbor Perspectives in Medicine

100

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Although p53 has long been known as the "guardian of the genome" with a role in tumor suppression in many tissues, the discovery of two p53 ancestral genes, p63 and p73, more than a decade ago has triggered a considerable amount of research into the role of these genes in skin development and diseases. In this review, we primarily focus on mechanisms of action of p53 and p63, which are the best-studied p53 family members in the skin. The existence of multiple isoforms and their roles as transcriptional activators and repressors are key to their function in multiple biological processes including the control of skin morphogenesis, regeneration, tumorigenesis, and response to chemotherapy. Last, we provide directions for further research on this family of genes in skin biology and pathology.

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Deconstructing the skin: cytoarchitectural determinants of epidermal morphogenesis

Cited by 413 publications

References 192 publications

Keratins as the main component for the mechanical integrity of keratinocytes

Keratins as the main component for the mechanical integrity of keratinocytes

Desmosomes and Intermediate Filaments: Their Consequences for Tissue Mechanics

p53/p63/p73 in the Epidermis in Health and Disease

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