Figure 5.

miR-24 promotes keratinocyte differentiation by repressing pro-proliferation factors and actin cytoskeleton modulators. In wt mice, miR-24 expression is confined to the suprabasal layers, where it represses the expression of Myc and E2F2, which determine when the cell exits the cell cycle, and PAK4, ArhGAP19 and Tks5, which promote actin cytoskeleton rearrangement. miR-24-dependent cell cycle exit and actin cytoskeleton rearrangement promote the proliferation/differentiation switch. In Tg K5::miR-24 mice, the ectopic expression of miR-24 in basal keratinocytes promotes early cell cycle exit and actin cytoskeleton rearrangement, which accelerates differentiation. The premature differentiation is confirmed by the expression of suprabasal markers in the basal layer. Tg K5::miR-24 mice demonstrate a severe body weight loss and have a thinner epidermis. Although the normal epidermal architecture is maintained, the epidermal compartments have a reduced number of cell layers³⁸