Hierarchical expression of desmosomal cadherins during stratified epithelial morphogenesis in the mouse

Desmosomes contain two heterogeneous families of specialized cadherins (desmogleins or Dsgs and desmocollins or Dscs), subtypes of which are known to be expressed in tissue-specific and differentiation-dependent patterns in adult epithelial tissues. To examine the temporal and spatial order in which the individual desmosomal cadherins are expressed during stratified epithelial development we have obtained partial cDNA clones of all six murine desmosomal cadherins and have carried out in situ hybridization analysis on E12.5 to E16.5 mouse embryos. The results indicate that the type 2, type 3 and type 1 desmosomal cadherin messages are not obligatorily expressed as pairs during stratified epithelial morphogenesis. Instead the individual genes appear to be transcribed in hierarchical, overlapping temporal and spatial patterns extending from DSG2 to DSC1. DSG2 was the most uniformly expressed message in all E12.5 epithelia, gradually becoming confined to the basal cell layers during epithelial stratification indicating that its transcription was restricted to undifferentiated cells. In contrast, DSC2 message was expressed variably in early epithelia and was strongly upregulated in the suprabasal cell layers during the stratification of wet-surfaced epithelia. DSC3 message was expressed before that of DSG3 in the dental and lingual epithelium where its spatial distribution matched that of DSG2, but after DSG3 in the non-glandular gastric epithelium. DSC3 transcripts became confined to the lower layers of stratifying epithelia but were usually less basally restricted than those of DSG2. Like DSC2, DSG3 mRNA was strongly upregulated in the suprabasal layers of wet-surfaced epithelia as they stratified. Upregulation of DSG1 message was temporally linked to that of DSG3 in all tissues apart from the non-glandular gastric epithelium. However, unlike DSG3, expression of DSG1 mRNA was maintained in the suprabasal layers of keratinizing epithelia and became restricted to the keratinizing inner root sheath in vibrissa follicles. DSC1 was always the last desmosomal cadherin message to be expressed and it was only detected in keratinizing tissues. Although there were tissue-specific differences in the temporal sequence of desmosomal cadherin transcription, the spatial order in which DSG and DSC messages were expressed during morphogenesis of all stratified epithelia was more consistent and correlated with the physical order of the genes at the desmosomal cadherin locus. These observations suggest the existence of an overall regulatory mechanism co-ordinating the hierarchical expression of DSG and DSC genes during epithelial differentiation and development.