Fig. 4.

Down-regulation of p63 is sufficient for HBC activation. (A and B) Comparison of HBC lineage trace in WT K5.CreER^T2 > LacZ mice (A and A′) and p63 cKO in K5.CreER^T2 > p63^fl/fl;R26R(LacZ) mice (B and B′) 2 wk after 50 mg/kg tamoxifen induction shows robust HBC activation in cKO vs. WT tissue. (C) Quantification of the proportion of non-HBCs derived from K5⁺ cells in WT [K5.CreER^T2 > R26R(LacZ)], heterozygote [HET, K5.CreER^T2 > p63^fl/+;R26R(LacZ)], and homozygote [HOMO, K5.CreER^T2 > p63^fl/fl;R26R(LacZ)] tissue, showing a relationship between p63 gene dosage and activation efficiency; *P < 0.0001; ANOVA with Bonferroni correction. (D–H) At 4 wk after tamoxifen (50 mg/kg) administration, HBCs activated by p63 cKO give rise to all the differentiated cell types of the OE, including K14⁻/PGP9.5⁻ GBCs situated between the HBC monolayer and the sensory neurons (arrows in D); Sox2⁺ columnar Sus cells situated at the apex of the epithelium (arrow in E); mature OMP⁺ OSNs (arrows in F); Bowman’s D/G units (arrow in G); and TrpM5⁺ microvillar cells (arrow in H). (I) In the K5.CreER^T2 > p63^fl/fl;R26R(LacZ) mice some LacZ⁺ HBCs (identified by their flattened shape) abutting the basal lamina retain expression of p63 protein, indicating that they have not undergone complete recombination of all three alleles. (Scale bars: 50 µm in A and B; 20 µm in A′, B′, and D–I.)