Converging Signaling Networks Drive Taste Bud Morphogenesis, Turnover, and Regeneration

Taste buds are continuously renewed sensory organs in which development, adult maintenance, and repair share overlapping molecular circuitry. During embryogenesis, WNT/β-catenin signaling promotes taste placode formation and placodal Shh expression, whereas SHH refines papilla spacing and restricts neighboring papilla formation. SOX2 functions as a taste-competence and progenitor-maintenance factor. In adults, LGR5/LGR6-RSPO-WNT signaling sustains progenitor activity, and gustatory neurons provide RSPO2 as a niche signal that maintains epithelial renewal. HH signaling from epithelial and neuronal sources further supports SOX2-dependent progenitor homeostasis. Lineage allocation is controlled by transcriptional programs that include POU2F3/SKN-1a for sweet, umami, and bitter type II taste receptor cells and ASCL1 with posterior-field NKX2-2 for type III presynaptic/sour cells. After denervation or irradiation, regeneration depends primarily on LGR5+/KRT14+ progenitors and may be supplemented, in specific injury contexts, by plasticity of a subset of K8-lineage taste receptor cells that acquire KRT14/SOX2/PCNA progenitor-like features. Key unresolved issues include the direct chromatin targets of taste lineage regulators (which remain to be defined by ChIP-seq in native taste progenitors), the identity of the type I cell selector, the contribution of dedifferentiation across injury models, and the extent to which mouse-derived networks are conserved in human taste biology.