Disease relevance of Dsc2

• In addition to these constitutive desmosomal components, representative for single-layered (simple) epithelia, the dural border cells of the arachnoid and about 60% of the meningiomas tested were positive for desmocollin 3 (Dsc3), a protein in epithelia taken as an indicator for differentiation [1].

High impact information on Dsc2

• In fact, most mutants die even before mature desmosomes are formed in the embryo, suggesting a new and unexpected role of Dsc3 during early development [2].
• Desmocollin 3 (Dsc3) is a transmembrane glycoprotein that belongs to the cadherin family of cell adhesion receptors [2].
• Previous reports have suggested that Dsc3 synthesis is largely restricted to stratified epithelia, and that it plays a role in the proper differentiation of these tissues during mammalian embryonic development [2].
• In addition, L cells co-expressing Dsg1, Dsc2a, and plakoglobin failed to aggregate [3].
• We have determined the full cDNA sequence of a murine desmocollin, the homologue of human and bovine type 2 desmocollins (DSC2), and studied its tissue distribution and expression in stratified epithelia [4].

Biological context of Dsc2

• An 8.5 day mouse embryo cDNA library was screened yielding overlapping clones which encoded the mouse DSC2 [4].
• Like other desmocollins, murine DSC2 has two products, Dsc2a and Dsc2b, produced by alternative splicing of a 46 bp exon which encodes 11 COOH-terminal aa followed by an in-frame stop codon [4].

Anatomical context of Dsc2

• In contrast, the level of desmosomal cadherin proteins, desmoglein 1/2 and desmocollin 2, were substantially upregulated and accompanied, ultrastructurally, by increased number and size of desmosomes [5].
• To understand better the processes by which Dsc expression is regulated in the epidermis, we have isolated Dsc3 and Dsc1 5'-flanking DNAs and analysed their activity in primary keratinocytes [6].
• DSC2 is ubiquitously expressed in epithelial tissues and the heart of adult mice and from the blastocyst stage of development [4].

Other interactions of Dsc2

• Here, we report the elucidation of the genomic structure of two mouse desmocollin genes, Dsc2 and Dsc3 [7].
• Our results reveal Foxn1 as an essential regulator of tissue assembly in the growing hair shaft and implicate Dsc2 as a downstream effector of this activity [8].
• One such gene encodes the desmosomal cadherin, Dsc2 [8].

Analytical, diagnostic and therapeutic context of Dsc2

• In situ hybridization shows that the gene is most strongly expressed suprabasally in stratified epithelia, similar to the expression of bovine DSC2 [4].

References