Overactive Wnt5a Signaling Disrupts Hair Follicle Polarity During Mouse Skin Development

The study demonstrated that overactive Wnt5a signaling disrupted hair follicle polarity in mouse skin development by causing misorientation of hair follicles. This effect was linked to signaling through the Frizzled 6 (Fzd6) receptor, as the misoriented phenotype was rescued by a heterozygous loss of Fzd6. Despite Wnt5a overexpression, the distribution of planar cell polarity (PCP) proteins remained unchanged, but transcriptional profiling identified potential target genes of the Wnt5a/Fzd6 signaling pathway. Interestingly, global or localized deletion of Wnt5a did not affect hair follicle orientation, suggesting that other Wnt proteins, which were highly expressed in developing skin, might also activate the Fzd6 pathway and work alongside Wnt5a to regulate skin polarization. This research provided new insights into the role of Wnt5a as an orienting cue in mouse skin PCP.