DIFFERENTIAL EXPRESSION PATTERN OF THE 3 FRINGE GENES IS ASSOCIATED WITH EPIDERMAL DIFFERENTIATION

Epidermal differentiation, as keratinocytes go through different layer s to the skin surface, may imply a differential activation of Notch tr ansmembrane proteins. In mouse, as recently shown in Drosophila, Notch activation by its ligands may be modulated by Fringe secreted protein s. Therefore, we cloned the mouse homolog of Radical-fng, synthesized riboprobes for Lunatic-fng, Manic-fng, and Radical-fng, and examined t heir expression during epidermal differentiation. Expression of all th ree genes is differentially activated during embryonic epidermal strat ification. Manic-fng and Lunatic-fng are expressed in the basal layer, whereas Lunatic-fng is expressed in the granular layer and Radical-fn g is restricted to the most differentiated nucleated layer. This expre ssion decreases by a few days postnatally and can be reactivated by re tinoic acid treatment, which triggers a new distribution of Fringe tra nscripts and a thickening of the granular layer. Therefore, Manic, Lun atic, and Radical Fringe by modulating the Notch pathway may play a ke y role in defining the different steps of keratinocyte differentiation .