A skin microRNA promotes differentiation by repressing 'stemness'

In stratified epithelial tissues, homeostasis relies on the self-renewing capacity of stem cells located within the innermost basal layer(1). As basal cells become suprabasal, they lose proliferative potential and embark on a terminal differentiation programme(2,3). Here, we show that microRNA- 203 is induced in the skin concomitantly with stratification and differentiation. By alteringmiR- 203' s spatiotemporal expression in vivo, we show that miR- 203 promotes epidermal differentiation by restricting proliferative potential and inducing cell- cycle exit. We identify p63 as one of the conserved targets of miR- 203 across vertebrates. Notably, p63 is an essential regulator of stem- cell maintenance in stratified epithelial tissues(4-9). We show that miR- 203 directly represses the expression of p63: it fails to switch off suprabasally when either Dicer1 or miR- 203 is absent and it becomes repressed basally when miR- 203 is prematurely expressed. Our findings suggest that miR- 203 defines a molecular boundary between proliferative basal progenitors and terminally differentiating suprabasal cells, ensuring proper identity of neighbouring layers.