Osorio et al. reveal that Runx1 has opposing effects on the Wnt pathway in the two layers of the embryonic skin, thus ensuring that hair follicles have plenty of stem cells.
A hair follicle goes through cycles of growth, regression, and inactivity. Hair follicle stem cells (HFSCs) provide fresh cells for the follicle's resurgence. The researchers previously showed that, in adult mice, Runx1 helps activate HFSCs and spurs them to divide. During embryonic development, Runx1 helps determine which cells will become hematopoetic stem cells that spawn new blood cells. Whether the protein performs a similar function for HFSCs during development was unknown.
Osorio et al. deleted Runx1 from either the epithelial or mesenchymal skin layers in embryonic mice. Loss of the protein from the skin's epithelium only delayed the appearance of hair follicles and progenitors of adult HFSCs, suggesting that Runx1 in this layer isn't essential for their development. Losing Runx1 from the mesenchyme, on the other hand, caused hair follicles to gradually degenerate and form oily cysts, indicating that the HFSCs adopted a sebaceous gland fate and failed to self-renew.
The Wnt signaling pathway orchestrates hair development. The team found that epithelial Runx1 revs up this pathway by boosting expression of Lef1, an activator of several Wnt-regulated genes. But in the mesenchyme, Runx1 quashed Wnt signaling. The researchers think that these opposing effects of Runx1 promote the origin and maintenance of HFSCs by controlling communication between the two skin layers.