Expression of the “Skin-Type” Desmosomal Cadherin DSC1 Is Closely Linked to the Keratinization of Epithelial Tissues During Mouse Development

King, Ian A.; O'Brien, Toby J.; Buxton, Roger S.

doi:10.1111/1523-1747.ep12582790

Cited by 43 publications

(55 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Dsc2 and Dsg2 are expressed in all desmosome-possessing tissues [25], whilst Dsc3, Dsg3, Dsc1 and Dsg1 are restricted to stratified epithelia [13,11]. Both Dsc1 and Dsg1, the ''skin type'' desmosomal cadherins, have been detected in all nucleated cells of epidermis [21], in the tongue [17,27], and in the keratinocyte compartment of human hair follicle [16].…”

Section: Introductionmentioning

confidence: 99%

Desmocollin 1 and desmoglein 1 expression in human epidermis and keratinizing oral mucosa: a comparative immunohistochemical and molecular study

et al. 2005

View full text Add to dashboard Cite

Epidermis and keratinizing oral mucosa (KOM) are effective barriers against a wide spectrum of insults. The optimal form of protection provided by each epithelium is determined also by the molecular composition of desmosomes. Up to now, the expression of the ''skin type'' desmosomal cadherins, i.e. desmocollin 1 (Dsc1) and desmoglein 1 (Dsg1), was correlated with the morphological features of keratinocyte terminal differentiation in epidermis, but not in KOM. The aim of the present study was to investigate Dsc1 and Dsg1 expression in adult human KOM compared to epidermis. Biopsies of epidermis and KOM were obtained from young healthy adults (n=6) and simultaneously processed for immunofluorescence analysis, postembedding immunogold electron microscopy (immunogold EM), and RT-PCR analysis. For molecular biology analysis, as a negative control, we considered human fibroblasts. By immunofluorescence and immunogold EM, Dsc1 labeling was not detected in any suprabasal layer of KOM, but it was present in the upper spinous/ granular layers of epidermis. Immunofluorescence and transmission electron microscopy analysis showed that (i) Dsg1 expression was evident in the spinous, granular, and horny layer of the oral epithelium and (ii) Dsg1 immunoreactivity was always lower in desmosomes between oral keratinocytes than in all epidermal junctions. RT-PCR analysis confirmed that in KOM Dsc1 gene expression was undetectable. On the whole, these observations suggest a weakened adhesion in KOM, allowing oral keratinocytes to undergo a faster transition throughout the living layers of the epithelium. The intrinsic and specific regulation of the molecular composition of desmosomes can contribute in defining a specific keratinocyte phenotype in KOM and in epidermis.

show abstract

Section: Introductionmentioning

confidence: 99%

Desmocollin 1 and desmoglein 1 expression in human epidermis and keratinizing oral mucosa: a comparative immunohistochemical and molecular study

et al. 2005

View full text Add to dashboard Cite

show abstract

“…All Dsc are synthesized in the epidermis, where they show very complex and overlapping expression patterns. Dsc1 is the predominant Dsc isoform synthesized in terminally differentiating keratinocytes of stratified epithelia (3,32,51). This protein is also present in the hair follicle, in particular the companion cell layer of the outer root sheath and the inner root sheath (e.g., see reference 42).…”

mentioning

confidence: 99%

“…Three Dsc isoforms (Dsc1 to Dsc3) have been identified in mammals (reviewed in references 26, 27, and 35) that show tissue-and cell type-specific expression patterns 3,15,32,[49][50][51]. All Dsc are synthesized in the epidermis, where they show very complex and overlapping expression patterns.…”

mentioning

confidence: 99%

“…The a and b variants differ only with respect to the COOH-terminal cytoplasmic amino acid sequences. The smaller b variants end with short amino acid sequences that are unique to these variants (11 amino acids in the case of Dsc1b [32]). The a variants have longer COOH termini (65 amino acids for Dsc1a) that show sequence homologies to classical cadherins, such as E-cadherin.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Assessment of Splice Variant-Specific Functions of Desmocollin 1 in the Skin

Cheng

Mihindukulasuriya

Den

et al. 2004

Molecular and Cellular Biology

View full text Add to dashboard Cite

Desmocollin 1 (Dsc1) is part of a desmosomal cell adhesion receptor formed in terminally differentiating keratinocytes of stratified epithelia. The dsc1 gene encodes two proteins (Dsc1a and Dsc1b) that differ only with respect to their COOH-terminal cytoplasmic amino acid sequences. On the basis of in vitro experiments, it is thought that the Dsc1a variant is essential for assembly of the desmosomal plaque, a structure that connects desmosomes to the intermediate filament cytoskeleton of epithelial cells. We have generated mice that synthesize a truncated Dsc1 receptor that lacks both the Dsc1a-and Dsc1b-specific COOH-terminal domains. This mutant transmembrane receptor, which does not bind the common desmosomal plaque proteins plakoglobin and plakophilin 1, is integrated into functional desmosomes. Interestingly, our mutant mice did not show the epidermal fragility previously observed in dsc1-null mice. This suggests that neither the Dsc1a-nor the Dsc1b-specific COOH-terminal cytoplasmic domain is required for establishing and maintaining desmosomal adhesion. However, a comparison of our mutants with dsc1-null mice suggests that the Dsc1 extracellular domain is necessary to maintain structural integrity of the skin.Desmosomes are adhesive cell-cell junctions that are formed in epithelia and certain other tissue types (reviewed in references 22, 25, 27, 30, 40, and 60). They are particularly abundant in stratified epithelia, such as the epidermis. The cytoplasmic surface of the desmosome is connected to the intermediate filament cytoskeleton, thereby establishing a three-dimensional transcellular scaffold of filament proteins that enables tissues to withstand mechanical stress.Impaired desmosome function has been found in patients with mutations in desmosomal genes (reviewed in references 13 and 25; see also reference 33) and patients who develop autoantibodies against desmosomal proteins (e.g., references in reference 62). Furthermore, the histopathology of the bacterium-induced skin disorders bullous impetigo and staphylococcal scaled-skin syndrome was attributed to enzymatic cleavage of the desmosomal transmembrane protein desmoglein 1 (2). In all of the examples listed above, severe skin disorders were observed, with clinical phenotypes ranging from palmoplantar keratoderma to skin blistering. Furthermore, mutations in the genes of the desmosomal plaque proteins plakoglobin and desmoplakin have been linked to cardiomyopathy (reviewed in reference 13).Genetically modified animals with mutations in desmosomal proteins were shown to develop phenotypes consistent with tissue fragility (1,5,6,14,28,33,37,38,67; see also references 21, 23, 24, and 58), demonstrating that desmosomes are crucial for the mechanical integrity and stability of certain tissues, in particular stratified epithelia. Furthermore, at least in some tissues, the correct temporal-spatial expression pattern of desmosomal proteins seems to be a prerequisite for the development of normal tissue and organ architecture (reviewed in reference 25).The...

show abstract

“…DSC2 is the desmocollin type first expressed in the developing mouse embryo from the 16/32 cell stage [13]. In contrast, type 1 and 3 isoforms have been detected only in certain stratified epithelia, DSC1 especially being restricted to the epidermis [9,14,15]. The genes coding for the desmocollins (DSC) and the desmogleins (DSG), six in total, have been shown to be closely linked on human chromosome 18q12.1 in two tandem arrays, one of desmocollins, the other of desmogleins [16,17].…”

mentioning

confidence: 99%

The Regulatory Region of the Human Desmocollin 3 Promoter Forms a DNA Four-Way Junction

Gadhavi¹,

Greenwood²,

Strom³

et al. 2001

Biochemical and Biophysical Research Communications

Self Cite

View full text Add to dashboard Cite

Expression of the “Skin-Type” Desmosomal Cadherin DSC1 Is Closely Linked to the Keratinization of Epithelial Tissues During Mouse Development

Cited by 43 publications

References 42 publications

Desmocollin 1 and desmoglein 1 expression in human epidermis and keratinizing oral mucosa: a comparative immunohistochemical and molecular study

Desmocollin 1 and desmoglein 1 expression in human epidermis and keratinizing oral mucosa: a comparative immunohistochemical and molecular study

Assessment of Splice Variant-Specific Functions of Desmocollin 1 in the Skin

The Regulatory Region of the Human Desmocollin 3 Promoter Forms a DNA Four-Way Junction

Contact Info

Product

Resources

About