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-dependen t patterns in adult epithelial tissues. To examine the temporal and sp atial order in which the individual desmosomal cadherins are expressed during stratified epithelial development we have obtained partial cDN A clones of ail six murine desmosomal cadherins and have carried out i n situ hybridization analysis on E12.5 to E16.5 mouse embryos. The res ults indicate that the type 2, type 3 and type 1 desmosomal cadherin m essages are not obligatorily expressed as pairs during stratified epit helial morphogenesis. Instead the individual genes appear to be transc ribed in hierarchical, overlapping temporal and spatial patterns exten ding 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 transcript ion was restricted to undifferentiated cells. In contrast, DSC2 messag e was expressed variably in early epithelia and was strongly upregulat ed in the suprabasal cell layers during the stratification of wet-surf aced epithelia. DSC3 message was expressed before that of DSG3 in the dental and lingual epithelium where its spatial distribution matched t hat of DSG2, but after DSG3 in the non-glandular gastric epithelium. D SC3 transcripts became confined to the lower layers of stratifying epi thelia but were usually less basally restricted than those of DSG2. Li ke DSC2, DSG3 mRNA was strongly upregulated in the suprabasal layers o f wet-surfaced epithelia as they stratified. Upregulation of DSG1 mess age was temporally linked to that of DSG3 in all tissues apart from th e non-glandular gastric epithelium. However, unlike DSG3, expression o f DSG1 mRNA was maintained in the suprabasal layers of keratinizing ep ithelia and became restricted to the keratinizing inner root sheath in vibrissa follicles. DSC1 was always the last desmosomal cadherin mess age to be expressed and it was only detected in keratinizing tissues. Although there were tissue-specific differences in the temporal sequen ce of desmosomal cadherin transcription, the spatial order in which DS G and DSC messages were expressed during morphogenesis of all stratifi ed epithelia was more consistent and correlated with the physical orde r of the genes at the desmosomal cadherin locus. These observations su ggest the existence of an overall regulatory mechanism co-ordinating t he hierarchical expression of DSG and DSC genes during epithelial diff erentiation and development.