Cellular Diversity and Regeneration in Taste Buds

Abstract

Taste buds are the sensory end organs for gustation, mediating sensations of salty, sour, bitter, sweet and umami as well as other possible modalities, e.g. fat and kokumi. Understanding of the structure and function of these sensory organs has increased greatly in the last decades with advances in ultrastructural methods, molecular genetics, and in vitro models. This review will focus on the cellular constituents of taste buds, and molecular regulation of taste bud cell renewal and differentiation.

Keywords: ATP; LGR5; SOX2; Sonic Hedgehog; Taste Receptors; WNT; adult stem cells; neurotransmitter.

Figure 1:

A. Reconstructions from a serial blockface scanning electron microscopic image series through a taste bud from a circumvallate papilla showing the characteristic morphology of the 4 canonical types of taste cells (Adapted from (Kinnamon and Finger 2019). Two Type IV cells aare shown (magenta). The smaller one at lower right is typical of a recently post-mitotic cell likely expressing SHH; the more elongate Type IV cell at left is relatively older and has begun differentiating into one of the other cell types. The surface of the epithelium is indicated by the gray horizontal line; the basal lamina by the gray bar at the bottom. B. Electron micrograph showing a dividing progenitor cell (PC) apposed to the basal lamina of the epithelium below a taste bud outlined in yellow. One of the daughter cells of this multipotent dividing cell may enter the taste bud to become a Type IV taste precursor cell. Roman numerals I-IV denote nuclei of identifiable taste cell types. Inset: Higher magnification of the PC showing the bilobed nucleus – a hallmark of telophase of cell division.

Fig. 2:

Schematic figures of lineage relationships and molecular regulators of taste bud cell renewal. A. Lingual progenitors (blue) sit at the basement membrane and are highly proliferative. Progenitors divide to replace themselves (circular arrows), as well as give rise to non-taste keratinocytes (grey - straight arrow, left), and SHH+ immediate taste precursor cells (light purple – straight arrow center). Each SHH+ cell can differentiate into a Type I (green), Type II (dark purple) or Type III (brick red) TBC. B. Production of non-taste keratinocytes (grey) from taste progenitors (blue) requires WNT and SOX2 function (noted along arrow connecting the 2 populations), while taste lineage production via SHH+ postmitotic precursors (light purple) requires WNT, SHH and SOX2 (noted along along arrow connecting the 2 populations). High levels of WNT (thick arrow) are hypothesized to be necessary for Type I TBC differentiation (green), while moderate WNT signaling may promote Type II TBC differentiation (dark purple)(see Barlow 2015). POU2F3 is required for Type II TBCs, while ASCL1 function is required for Type III TBCs (brick red). Gene products in all capitals aligned with lineage arrows indicate functional role in TBC renewal, genes listed in beneath or adjacent to cell lineage steps in sentence case are expressed in each cell population.