D. R. Roop

Sequential Changes in Gene Expression during Epidermal Differentiation

Genes encoding the major proteins expressed in mouse epidermis have been isolated and characterized. Using a combination of in situ hybridization with RNA probes, which are specific for individual mRNA’s, and indirect immunofluorescence with specific antisera, which were elicited with synthetic peptides corresponding to unique sequences within each protein, it is possible to show that these genes belong to at least four subsets: those expressed predominantly in the proliferating basal layer of the epidermis (keratins 5 and 14); those expressed predominantly in the differentiated suprabasal spinous layer and to a less extent the granular layer (keratins 1 and 10); those initially expressed in the upper spinous layer but most prominently in the granular layer (the gene encoding the precursor for filaggrin, a protein thought to promote keratin filament aggregation and the gene encoding a major component of the comified envelope) and those only expressed under hyperproliferative conditions (keratin 6). In order to identify sequences regulating the expression of these genes, transgenic mice have been produced which contain one of the human differentiation-associated keratin genes (K1). The human K1 gene is located within a 12 kilobase (Kb) fragment and is flanked by 2 Kb upstream and 3 Kb downstream. This DNA fragment contains sufficient sequence information for tissue-specific, developmental-specific and differentiation-specific expression.