ZF atrophy triggers Shh overexpression and increases the number of Shh-descendant cells. (A) Heatmap showing selected genes of the HH signature. For each time point, n = 4. (B) β-Galactosidase expression (in blue) in Shh-LacZ reporter mice. An increase of cell Shh+ is evident following dexamethasone treatment and recovery. For each time point, n = 5. (C) Schematic of treatment protocol for ShhCreERT2-R26REGFP mice. Mice were treated with vehicle (control mice) or dexamethasone for 14 days and injected with tamoxifen both on the last day of dexamethasone treatment and on the following day. Adrenals were harvested 1 day later at R0 and at R3, R7, and R14. (D) Quantification of EGFP+ cells per high-powered field normalized to number of nuclei. Error bars represent standard error of the mean. *P < 0.05; **P < 0.01; and ***P < 0.001. For each time point, n = 5. (E) Immunofluorescent staining of adrenals from ShhCreERT2-R26REGFP mice. EGFP+ cells (green) indicate Shh lineage. Nuclei stained with DAPI (in blue). For each time point, n = 5. Scale bars: 100 μm. Dex, dexamethasone; Tam, tamoxifen.