MicroRNAs are important for the regulation of gene expression in a vast array of processes. In the skin, miR-203 has been shown to be crucial for the proper differentiation of the interfollicular progenitor cells, although the specific mechanism of this has remained elusive. In this issue (), Rui Yi and colleagues investigate the precise timing of miR-203 activation during epidermal differentiation. They show that miR-203 is transcriptionally activated in the differentiating progeny of interfollicular progenitor cells upon asymmetric cell division. Using keratinocytes derived from miR-203-inducible mice, the authors found that miR-203 functions to promote an immediate exit from the cell cycle, leading to a complete loss of self-renewal after just 72 hours. They further identify a multitude of novel miR-203 targets in vivo, and demonstrate that co-repression by miR-203 of many of these, including Skp2, Msi2 and p63, is necessary for the function of miR-203 in inhibiting self-renewal. These data provide novel insights into the widespread role of miR-203 in differentiating interfollicular progenitor cells in the skin.
