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Desmoglein isoform distribution affects stratum corneum structure and function.

Elias PM, Matsuyoshi N, Wu H, Lin C, Wang ZH, Brown BE, Stanley JR - J. Cell Biol. (2001)

Bottom Line: Ultrastructure of the stratum corneum showed premature loss of cohesion of corneocytes.This dysadhesion of corneocytes and its contribution to increased transepidermal water loss was confirmed by tape stripping.These data demonstrate that differential expression of desmoglein isoforms affects the major function of epidermis, the permeability barrier, by altering the structure of the stratum corneum.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, University of California San Francisco, San Francisco, California 94143, USA.

ABSTRACT
Desmogleins are desmosomal cadherins that mediate cell-cell adhesion. In stratified squamous epithelia there are two major isoforms of desmoglein, 1 and 3, with different distributions in epidermis and mucous membrane. Since either desmoglein isoform alone can mediate adhesion, the reason for their differential distribution is not known. To address this issue, we engineered transgenic mice with desmoglein 3 under the control of the involucrin promoter. These mice expressed desmoglein 3 with the same distribution in epidermis as found in normal oral mucous membranes, while expression of other major differentiation molecules was unchanged. Although the nucleated epidermis appeared normal, the epidermal stratum corneum was abnormal with gross scaling, and a lamellar histology resembling that of normal mucous membrane. The mice died shortly after birth with severe dehydration, suggesting excessive transepidermal water loss, which was confirmed by in vitro and in vivo measurement. Ultrastructure of the stratum corneum showed premature loss of cohesion of corneocytes. This dysadhesion of corneocytes and its contribution to increased transepidermal water loss was confirmed by tape stripping. These data demonstrate that differential expression of desmoglein isoforms affects the major function of epidermis, the permeability barrier, by altering the structure of the stratum corneum.

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Dsg 3 in the superficial epidermis of transgenic mice results in premature dissolution of desmosomes and cleft formation in the stratum corneum. (A) Dissolution of desmosomes begins at the stratum granulosum (SG)–stratum corneum (SC) interface. Desmosomal detachment (single arrows) results in cleft formation (*) at all levels of the stratum corneum. D, normal-appearing desmosomes. (B) Normal-appearing desmosomes in control stratum corneum. (C) Normal mucous membrane (lip) also reveals early cleft formation. Note small (small *) clefts at SG–SC interface and larger clefts (large *) at higher levels. Bar: 0.5 μm (A and B), 1 μm (C). Osmium tetroxide postfixation.
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Figure 5: Dsg 3 in the superficial epidermis of transgenic mice results in premature dissolution of desmosomes and cleft formation in the stratum corneum. (A) Dissolution of desmosomes begins at the stratum granulosum (SG)–stratum corneum (SC) interface. Desmosomal detachment (single arrows) results in cleft formation (*) at all levels of the stratum corneum. D, normal-appearing desmosomes. (B) Normal-appearing desmosomes in control stratum corneum. (C) Normal mucous membrane (lip) also reveals early cleft formation. Note small (small *) clefts at SG–SC interface and larger clefts (large *) at higher levels. Bar: 0.5 μm (A and B), 1 μm (C). Osmium tetroxide postfixation.

Mentions: The epidermal nucleated cell layers of the living epidermis showed comparable normal ultrastructure, including desmosomal substructure, in transgenic and nontransgenic littermates. However, the epidermal stratum corneum of transgenic animals differed strikingly from that of nontransgenic littermates. Normally, with the transition from the stratum granulosum to the stratum corneum, and then, again, in the superficial stratum corneum, the desmosome changes structure (Menon and Elias 1997; Fartasch et al. 1993). In the nucleated layer, it is seen as two opposing dense plaques within the cell with an electron lucent center. In the stratum corneum, it abruptly becomes an electron dense intercellular structure (Fig. 5 B, arrows). In the normal stratum corneum, these desmosomal structures are well maintained with closely opposed cells until near the surface of the skin when the desmosomal structures degenerate and the corneocytes separate (Odland 1991). In contrast to this normal structure, at the stratum granulosum–stratum corneum interface and extending to the lowermost stratum corneum in transgenic mice, we noted premature dissolution of desmosomes with early cleft formation between adjacent corneocytes (compare Fig. 5A with B). This finding in the transgenic epidermal stratum corneum was similar to the early dissolution of desmosomes that occurs in stratum corneum of normal oral mucous membrane (Fig. 5 C). Premature dissolution of desmosomes with cleft formation was even more obvious in ruthenium tetroxide postfixed tissues, where the relationship of the clefts to the extracellular lamellar matrix could be appreciated (Fig. 6). These findings are consistent with loss of barrier function from early loss of corneocyte adhesion in these transgenic animals.


Desmoglein isoform distribution affects stratum corneum structure and function.

Elias PM, Matsuyoshi N, Wu H, Lin C, Wang ZH, Brown BE, Stanley JR - J. Cell Biol. (2001)

Dsg 3 in the superficial epidermis of transgenic mice results in premature dissolution of desmosomes and cleft formation in the stratum corneum. (A) Dissolution of desmosomes begins at the stratum granulosum (SG)–stratum corneum (SC) interface. Desmosomal detachment (single arrows) results in cleft formation (*) at all levels of the stratum corneum. D, normal-appearing desmosomes. (B) Normal-appearing desmosomes in control stratum corneum. (C) Normal mucous membrane (lip) also reveals early cleft formation. Note small (small *) clefts at SG–SC interface and larger clefts (large *) at higher levels. Bar: 0.5 μm (A and B), 1 μm (C). Osmium tetroxide postfixation.
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Related In: Results  -  Collection

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Figure 5: Dsg 3 in the superficial epidermis of transgenic mice results in premature dissolution of desmosomes and cleft formation in the stratum corneum. (A) Dissolution of desmosomes begins at the stratum granulosum (SG)–stratum corneum (SC) interface. Desmosomal detachment (single arrows) results in cleft formation (*) at all levels of the stratum corneum. D, normal-appearing desmosomes. (B) Normal-appearing desmosomes in control stratum corneum. (C) Normal mucous membrane (lip) also reveals early cleft formation. Note small (small *) clefts at SG–SC interface and larger clefts (large *) at higher levels. Bar: 0.5 μm (A and B), 1 μm (C). Osmium tetroxide postfixation.
Mentions: The epidermal nucleated cell layers of the living epidermis showed comparable normal ultrastructure, including desmosomal substructure, in transgenic and nontransgenic littermates. However, the epidermal stratum corneum of transgenic animals differed strikingly from that of nontransgenic littermates. Normally, with the transition from the stratum granulosum to the stratum corneum, and then, again, in the superficial stratum corneum, the desmosome changes structure (Menon and Elias 1997; Fartasch et al. 1993). In the nucleated layer, it is seen as two opposing dense plaques within the cell with an electron lucent center. In the stratum corneum, it abruptly becomes an electron dense intercellular structure (Fig. 5 B, arrows). In the normal stratum corneum, these desmosomal structures are well maintained with closely opposed cells until near the surface of the skin when the desmosomal structures degenerate and the corneocytes separate (Odland 1991). In contrast to this normal structure, at the stratum granulosum–stratum corneum interface and extending to the lowermost stratum corneum in transgenic mice, we noted premature dissolution of desmosomes with early cleft formation between adjacent corneocytes (compare Fig. 5A with B). This finding in the transgenic epidermal stratum corneum was similar to the early dissolution of desmosomes that occurs in stratum corneum of normal oral mucous membrane (Fig. 5 C). Premature dissolution of desmosomes with cleft formation was even more obvious in ruthenium tetroxide postfixed tissues, where the relationship of the clefts to the extracellular lamellar matrix could be appreciated (Fig. 6). These findings are consistent with loss of barrier function from early loss of corneocyte adhesion in these transgenic animals.

Bottom Line: Ultrastructure of the stratum corneum showed premature loss of cohesion of corneocytes.This dysadhesion of corneocytes and its contribution to increased transepidermal water loss was confirmed by tape stripping.These data demonstrate that differential expression of desmoglein isoforms affects the major function of epidermis, the permeability barrier, by altering the structure of the stratum corneum.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, University of California San Francisco, San Francisco, California 94143, USA.

ABSTRACT
Desmogleins are desmosomal cadherins that mediate cell-cell adhesion. In stratified squamous epithelia there are two major isoforms of desmoglein, 1 and 3, with different distributions in epidermis and mucous membrane. Since either desmoglein isoform alone can mediate adhesion, the reason for their differential distribution is not known. To address this issue, we engineered transgenic mice with desmoglein 3 under the control of the involucrin promoter. These mice expressed desmoglein 3 with the same distribution in epidermis as found in normal oral mucous membranes, while expression of other major differentiation molecules was unchanged. Although the nucleated epidermis appeared normal, the epidermal stratum corneum was abnormal with gross scaling, and a lamellar histology resembling that of normal mucous membrane. The mice died shortly after birth with severe dehydration, suggesting excessive transepidermal water loss, which was confirmed by in vitro and in vivo measurement. Ultrastructure of the stratum corneum showed premature loss of cohesion of corneocytes. This dysadhesion of corneocytes and its contribution to increased transepidermal water loss was confirmed by tape stripping. These data demonstrate that differential expression of desmoglein isoforms affects the major function of epidermis, the permeability barrier, by altering the structure of the stratum corneum.

Show MeSH
Related in: MedlinePlus