Prox1 maintains taste bud structure via inhibition of apoptosis

Abstract Taste buds are maintained by continuous cell renewal, receiving a steady influx of postmitotic cells from the surrounding epithelial region. Within taste buds, Type I, II, and III cells continuously differentiate from Type IV postmitotic precursor cells and are removed via apoptosis. These processes are likely governed by various transcription factors. Among the transcription factors expressed in taste buds, Prox1 , a homeobox transcription factor, is the only factor expressed in all taste bud cells including precursor cells. However, its role in taste buds remains unclear. Here, we investigate the function of Prox1 in taste bud cell turnover using conditional knockout (cKO) mice. In Prox1 cKO mice, all Type I, II, and III cells were significantly reduced, resulting in approximately half the total cell number per taste bud compared to wild-type mice, while Type IV cell numbers remained comparable. Apoptosis of taste bud cells nearly doubled, leading to a shortened lifespan of taste bud cells. EdU pulse-labeling experiments revealed a biphasic decline in EdU(+) taste bud cells in Prox1 cKO mice, indicating that Prox1 knockout increases the fraction of cells that die shortly after differentiating into taste bud cells. The surviving cells still exhibited a shorter lifespan than that of wild-type mice. We also observed previously unreported structural alterations within taste buds caused by enhanced apoptosis using whole-mount analysis. These results demonstrate that Prox1 contributes to the maintenance of taste bud structure by regulating the lifespan of taste bud cells, highlighting its essential role in taste bud homeostasis.