Figure 6. WNT and BMP signalings modulate ear HF hyper-refractory state.
(A–C) Transcriptomes of first telogen ear skin, first telogen dorsal skin and ear cartilage/muscle complex are distinct, as revealed by PCA analysis (A). They contain 1334 differentially expressed genes (B), spanning distinct gene ontologies (C). (D, E) These tissues show differential expression of multiple ligands and antagonists for several major signaling pathways, prominently WNT and BMP. Putative activators are in green and putative inhibitors are in red. For each gene, relative fold changes for ear skin over dorsal skin and cartilage/muscle complex over dorsal skin expression levels are indicated. Select genes are highlighted. (F, F’) BRE-gal reporter reveals high BMP activity in telogen ear HFs and in the adjacent cartilage/muscle complex (n = 8). (G, G’) Axin2-lacZ reporter reveals near absence of WNT activity in ear HFs and cartilage/muscle complex. Seldom, sites of dermal reporter activity can be found (n = 8). (H–H’’) Compared to wild type mice (n = 4) (H), ears of Krt14-Noggin (n = 4) (H’) and Krt14-Wnt7a mice (n = 4) (H’’) show prominent increases in spontaneous anagen frequency. Cumulative heatmaps from four individual ear samples are shown. Also see Appendix 1—figure 28. Scale bars: F, G – 500 um; F’, G’ – 100 um.