Figure 4. BMP and WNT signaling differences underlie regionally specific telogen phase duration.
(A–B’’) PCA analysis reveals largely non-overlapping transcriptomic trajectories across six hair cycle stages in chin (B), ventral (B’) and dorsal domains (B’’). Combined, deconstructed PCA plots are shown with all data points marked as grey dots and domain-specific data points outlined and color-coded. Color-coding is based on the hair cycle timeline from Appendix 1—figure 14A; transcriptomic trajectories are drawn with dark lines. (C) Deconstructed PCA plot for refractory (early second) telogen is shown with domain-specific data points highlighted and color-coded based on the schematic drawing on A. (D–F) Analysis of refractory telogen data identified 1407 differentially expressed genes across the three domains (D), with each domain showing enrichment for distinct gene ontologies (E). Multiple putative hair cycle activator and inhibitor genes show domain-specific differential expression (F). Putative activators are in green and putative inhibitors are in red. For each gene, relative fold changes for ventral over chin and dorsal over chin expression levels are indicated. Genes that show cyclic expression patterns are highlighted with blue. See additional expression data analysis on Appendix 1—figures 14–19 and in Dataset 2. Asterisk marks non-canonical WNT ligand. (G, H) Analysis of Axin2-lacZ skin during second telogen reveals faster activation of WNT signaling in chin and ventral HFs over dorsal HFs. At P36 majority of HFs in chin and ventral skin have WNT-active DPs. In dorsal skin, the number of HFs with WNT-active DPs is low at P36, but increases by P42. (I) Analysis of P42 BRE-gal skin shows that many more dorsal HFs have BMP-active bulges as compared to chin and ventral HFs. Also see Appendix 1—figure 22. (J) Overexpression of Wnt7a results in disruption of ventral-to-dorsal hair growth wave dominance and spontaneous anagen appears in the dorsal domain at P60. (K) Overexpression of Bmp4 results in stalled ventral-to-dorsal hair growth wave spreading and patchy, asymmetric hair growth at P57. Scale bars: G-I – 200 um, J-K – 500 um.