Figure 4.

FGP with signaling niches or compartments. Building on Figures 1 and 2, four niches are proposed for Hh signaling in specific FGP cell compartments. (a) Niche 1 is within and around the taste bud, including taste bud and perigemmal cells. Signaling from Shh⁺ taste bud cells to HH-responding, perigemmal proliferative cells, extragemmal apical cells, and extragemmal apical nerves is proposed. (b) Niche 2 represents the highly proliferative, basal epithelial cells at the base or bottom of the FGP walls, including Gli1⁺ Hh-responding cells that are the progenitors of taste bud cells, perigemmal cells, and stratified keratinocytes of the FGP. These cells are positioned over stromal cells and lingual innervation. (c) In the apical FGP core and base of the taste bud, Niche 3 includes Shh⁺ basal taste bud cells and the basal lamina, taste cell bipolar extensions to the basal lamina, Hh-responding cells of the stroma, nerve fibers and Shh⁺ nerve fibers, and fibroblasts with filopodia in close association with the basal lamina. Multiple Shh signaling exchanges are likely, including those to the stromal compartment, based on taste bud-derived Shh secretion and sequestration of Shh ligand by basal lamina components. This also provides a signaling domain for stromal cells to regulate epithelial progenitors, and importantly, a particular perineural environment around lingual and taste nerve fibers to regulate FGP and taste bud progenitor and stem cells. (d) Niche 4 is in basal epithelial cells at the base or near bottom of the FILIFP, including proliferative cells seated on the basal lamina positioned over vimentin⁺ stromal cells and nerve fibers. Bmi1⁺, Tcf3⁺, and Gli2⁺ cells include progenitors for keratinocytes of the interpapilla epithelium and FILIFP. Abbreviations: FGP, fungiform papillae; FILIFP, spinous filiform papillae; Hh, Hedgehog; Shh, Sonic Hedgehog