Sonic hedgehog–expressing basal cells are general post‐mitotic precursors of functional taste receptor cells

Background: Taste buds contain ∼60 elongate cells and several basal cells. Elongate cells comprise three functional taste cell types: I, glial cells; II, bitter/sweet/umami receptor cells; and III, sour detectors. Although taste cells are continuously renewed, lineage relationships among cell types are ill‐defined. Basal cells have been proposed as taste bud stem cells, a subset of which express Sonic hedgehog (Shh). However, Shh+ basal cells turn over rapidly suggesting that Shh+ cells are post‐mitotic precursors of some or all taste cell types. Results: To fate map Shh‐expressing cells, mice carrying ShhCreERT2 and a high (CAG‐CAT‐EGFP) or low (R26RLacZ) efficiency reporter allele were given tamoxifen to activate Cre in Shh+ cells. Using R26RLacZ, lineage‐labeled cells occur singly within buds, supporting a post‐mitotic state for Shh+ cells. Using either reporter, we show that Shh+ cells differentiate into all three taste cell types, in proportions reflecting cell type ratios in taste buds (I > II > III). Conclusions: Shh+ cells are not stem cells, but are post‐mitotic, immediate precursors of taste cells. Shh+ cells differentiate into each of the three taste cell types, and the choice of a specific taste cell fate is regulated to maintain the proper ratio within buds. Developmental Dynamics 243:1286–1297, 2014. © 2014 Wiley Periodicals, Inc. Key findings Taste buds are heterogeneous collections of functionally distinct cells, which are continually renewed by proliferating epithelial cells outside of buds. In addition to elongate taste receptor cells, taste buds possess round, basally situated cells, which express the gene, Sonic hedgehog (Shh). We show here that Shh‐expressing cells are a transient cell type which differentiate into all 3 of the functional taste cell types (I, II and III) in mature buds, and do so in proportion to the stable ratios of these taste cell types in taste buds (I>II>III).