REGULATION OF EPIDERMAL DIFFERENTIATION BY A DISTAL-LESS HOMEODOMAIN GENE

The Distal-less-related homeodomain gene Dlx3 is expressed in terminal ly differentiated murine epidermal cells. Ectopic expression of this g ene in the basal cell layer of transgenic skin results in a severely a bnormal epidermal phenotype and leads to perinatal lethality. The basa l cells of affected mice ceased to proliferate, and expressed the prof ilaggrin and loricrin genes which are normally transcribed only in the latest stages of epidermal differentiation. All suprabasal cell types were diminished and the stratum corneum was reduced to a single layer . These data indicate that Dlx3 misexpression results in transformatio n of basal cells into more differentiated keratinocytes, suggesting th at this homeoprotein is an important regulator of epidermal differenti ation.