Dependence of hair follicle orientation on Fz6 expression in the inter-follicular epidermis. (A) Left panel: expression of Fz6 in both hair follicle cells and inter-follicular epidermis assessed by X-gal staining of a cross-section from an E15.5 Fz6lacZ embryo. Right panels: Shh-Cre recombines the Hprt-LSL-tdT reporter in hair follicle epithelial cells but not in the surface epidermis. The skin surface is marked by dashed lines. Scale bars, 50 µm. (B) Exclusive expression or knockout of Fz6 in hair follicle epithelial cells by Shh-Cre. The schematics show a whole-mount view of back skin with hair follicles (circles) and the surrounding surface epidermis. Anterior is to the left, and the territory of Fz6 expression is indicated in red. Lower panels: Immunostaining for Fz6 and E-cadherin confirms the territorial expression patterns diagrammed above. Arrows, epidermis; arrowheads, hair follicles. Scale bar, 100 µm. (C) Flat mount images of back skin at P3 from mice with the same four genotypes as shown in panel (B). Beneath each image is the quantification of follicle orientations relative to the anterior-posterior (A–P) axis. Scale bar, 0.5 mm.