Dermal Wnt/β-Catenin Activation Tunably Controls Hair Follicle Initiation

The document reports on a study that investigated the role of Wnt/β-catenin signaling in hair follicle (HF) initiation. The researchers used in vivo genetic mouse models to demonstrate that the number of β-catenin-activated (Wnt+) dermal cells prior to HF initiation can tunably determine the number of HF epithelial cells and associated dermal niche cells that form. Single-cell RNA sequencing analysis of embryonic skin indicated that non-dermal condensate (DC) Wnt-active dermal cells are on a differentiation trajectory toward a DC cell fate. Genetic lineage tracing confirmed that Wnt-active dermal cells present before HF initiation contribute to DC cells. Additionally, mutant HFs were found to be composed selectively of wildtype Wnt-active dermal cells, suggesting a cell-autonomous requirement for Wnt signaling in DC formation. Live imaging of embryonic skin explants showed that Wnt-active dermal cells migrate to form the DC and that dermal Wnt regulates actomyosin activity. These findings suggest that dermal Wnt activation controls DC formation by regulating dermal cell migration and that an early patterned pre-DC population may direct HF epithelial cell fate specification.