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. Author manuscript; available in PMC: 2023 Jul 1.
Published in final edited form as: Dev Dyn. 2022 Feb 18;251(7):1175–1195. doi: 10.1002/dvdy.456

Figure 7. Elimination of Gli1+ cells alone after HH pathway inhibition is not sufficient for the induction of ectopic HHIP in fungiform papilla (FP) and expression of ectopic HHIP is not directly impeding FP recovery after withdrawing HH pathway inhibition.

Figure 7.

(A-C) Antibody detection of endogenous HHIP (red) and taste bud (TB) cells (K8, green) after 5d whole body Smo deletion. Three categories of FP/TB: Typical FP/TB, Atypical FP/TB and Atypical FP/No TB are assessed. Percentage numbers are quantification of the three FP/TB types in a half tongue (total FP = 28). (A’-C’) X-Gal staining in the same sections demonstrates elimination of Gli1lacZ HH-responding cells from FP basal and perigemmal cell regions in all the three FP/TB types. HHIP expression in Atypical FP with or without TB (arrows) and not in Typical FP/TB suggests a requirement of both SHH and Gli1 reduction for ectopic HHIP expression. Asterisks in B denote non-specific staining post X-Gal reactions. Dotted lines outline the base of the epithelium. Scale bar in A applies to all images. (D-F) Antibody detection of endogenous HHIP (red) and TB cells (K8, green) after Vehicle and 16d sonidegib treatment followed by 14 days Recovery (discontinuation of drug). Percentage numbers are quantification of Typical FP/TB and Atypical FP/No TB during Recovery from previous findings4. There is no HHIP expression in Typical FP/TB in Vehicle (D) or after Recovery (E). Ectopic HHIP expression is apparent in Atypical FP/No TB even after stopping the drug treatment for 14 days (F). (G-I) X-Gal staining in Gli1lacZ reporter mouse in Vehicle and Sonidegib treated Recovery group showed usual Gli1lacZ expression, in FP basal, perigemmal and stromal cells, in Vehicle (G) and in the recovered Typical FP/TB (H). In Atypical FP/No TB, while Gli1lacZ expression is not restored in FP epithelium (I) HHIP expression is maintained at the FP apex (F). Thus, if Gli1lacZ+ cells are resumed during recovery the ectopic HHIP expression is simultaneously lost, and when there is no Gli1lacZ activity HHIP is retained. Dotted lines outline the base of the epithelium. Yellow dotted lines label the surface of epithelium. Scale bar applies to all images.