Regional Differences in Dorsal Skin Determine the Rate of Adhesive Material-Induced Hair Regeneration

Abstract

Dorsal skin is widely used in mouse wound-healing, dermatitis, and hair-cycle models, but is often treated as a uniform site. We investigated whether adhesive material (cyanoacrylate)-induced hair regeneration, a model we previously reported, differs by position within the dorsal skin. Adhesive material was applied to four regions along the cranial-to-caudal axis of the mouse dorsal skin. Hair regrowth appeared earlier at the cranial sites than at the caudal sites, and this difference persisted through late anagen and the anagen-to-catagen transition. In contrast, hair regrowth after full-thickness skin excision was slower, smaller in area, and less reproducible than that after adhesive material application. Expression of Hox genes, including Hoxa9, Hoxb9, Hoxc9, Hoxa10, and Hoxc10, was higher at the caudal sites than at the cranial sites but did not correlate with the timing of hair regrowth. RNA sequencing of intact skin from the cranial and caudal sites revealed distinct baseline profiles, including differences in the Wnt inhibitor Sfrp4 and the adipogenic genes Ppar{gamma} and Fabp4. Early after adhesive material application, histological changes and the expression of inflammation- and tissue-repair-related genes also differed between the cranial and caudal skin. These findings indicate that mouse dorsal skin is not a uniform experimental field and that cranial-to-caudal position should be considered when designing and interpreting hair-regeneration and wound-healing experiments in mice.