Hairless and Wnt Signaling: Allies in Epithelial Stem Cell Differentiation

The document from 2006 explores the importance of the Hairless (HR) protein in hair follicle cycling and the differentiation of epithelial stem cells, highlighting its role as a nuclear receptor corepressor and its interaction with Wnt signaling pathways. It was found that mutations in HR lead to hair loss in both mice and humans, indicating its significance in hair cycle regulation via gene expression. The study reviewed reveals that HR's corepressor activity is vital for its function in vivo and identifies a potential Wnt inhibitor regulated by HR. The research also shows that HR regulates the expression of Wise, a Wnt signaling inhibitor, which is essential for the proper timing of Wnt signaling in hair cycling. Experiments with HR mutants lacking corepressor activity confirmed that this function is necessary for hair cycling, thus connecting corepressor function to the observed phenotype. The document suggests that HR operates through the vitamin D receptor in the skin, as VDR mutations also result in hair loss. The conclusion is that HR's repressor role is crucial for the regulation of hair cycling.